Molecular Oncology Almanac Patient Report

Molecular Oncology Almanac classifies each curated assertion with a "predictive implication" that describes the strength of evidence for a given relationship between a molecular feature and clinical action. The evidence levels used are:

Evidence level	Description
FDA-Approved	The Food and Drug Association (FDA) recognizes an association between the alteration and recommended clinical action.
Guideline	This relationship is catalogued as a guideline for standard of care treatment.
Clinical trial	The alteration is or has been used as an eligibility criterion for a clinical trial.
Clinical evidence	The relationship is reported in a clinical study that did not directly involve a clinical trial.
Preclinical evidence	This relationship is reported in a study involving mice, cell lines, or patient derived models.
Inferential evidence	The relationship is inferred as a result of mathematical modeling or an association between molecular features.

Molecular Oncology Almanac evaluates alterations based on how closely they match an alteration-action relationship, as given by catalogued assertions.

To illustrate by example, consider matching variants against the assertion that BRAF p.V600E suggests sensitivity to Vemurafenib:

Bin	Example	Description
Putatively Actionable	BRAF Mutation Missense p.V600E	An exact match
Investigate Actionability - High	BRAF Mutation Missense p.V500L	Gene (feature), feature type, alteration type all match but not the specific alteration
Investigate Actionability - Low	BRAF Mutation Frameshift p.V500fs	Gene (feature) and feature type match but not the alteration type or alteration
Biologically Relevant	BRAF Amplification	Gene (feature) match only

Molecular Oncology Almanac leverages several datasources to evaluate the predictive implication of each feature. Datasources and versions used to create this report are:

Datasource	Release
Molecular Oncology Almanac - Interpreter	0.2.0
Molecular Oncology Almanac - Database	0.4.7
American College of Medical Genetics and Genomics - Secondary Findings	2.0
Cancer Gene Census	85
Cancer Hotspots	2.0
3D Hotspots	1.0
ClinVar	Accessed October 25th, 2018
COSMIC	85
ExAC	1.0
Molecular Signatures Database (MSigDB)
Oncotree	Accessed June 6th, 2018

Molecular Oncology Almanac

Patient Report

Generated on: Aug 06 2020

Patient Information

Identifiers

Patient ID:	example
Tumor Barcode:	example_patient_tumor
Normal Barcode:	example_patient_normal

Disease

Code:	SKCM
Ontology:	Cutaneous Melanoma
Stage:	Metastatic

Metrics

Tumor Purity:	0.85
Tumor Ploidy:	4.02
Microsatellite Stability:	MSI-High

Actionability Report

About:

Variants and Features associated with Therapeutic Sensitivity

Predictive Implication

Feature Type

Feature

Therapy & Rationale

FDA-Approved
Putatively Actionable

The following assertion was the strongest match to the observed molecular feature.

Evidence:	FDA-Approved
Molecular feature:	BRAF p.V600E (Missense)
Assertion:	Sensitivity to Dabrafenib + Trametinib in Melanoma (MEL)

The U.S. Food and Drug Administration (FDA) granted approval to dabrafenib in combination with trametinib for the treament of patients with unresectable or metastatic melanoma (MEL) with BRAF V600E or V600K mutation, as detected by an FDA-approved test. [source]

The following assertions are equivalent matches within this patient's ontology or stronger in another cancer type.

Molecular feature & evidence	Assertion & rationale
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Dabrafenib + Trametinib in Melanoma (MEL) The U.S. Food and Drug Administration (FDA) granted approval to dabrafenib in combination with trametinib for the adjuvant treament of patients with unresectable or metastatic melanoma (MEL) with BRAF V600E or V600K mutation, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection. [source]
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Dabrafenib + Trametinib in Non-Small Cell Lung Cancer (NSCLC) The U.S. Food and Drug Administration (FDA) granted approval to dabrafenib in combination with trametinib for the treament of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E, as detected by an FDA-approved test. [source]
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Dabrafenib in Melanoma (MEL) The U.S. Food and Drug Administration (FDA) granted approval to dabrafenib as a single agent for the treament of patients with unresectable or metastatic melanoma (MEL) with BRAF V600E mutation, as detected by an FDA-approved test. [source]
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Trametinib in Melanoma (MEL) The U.S. Food and Drug Administration (FDA) granted approval to trametinib as a single agent for the treament of patients with unresectable or metastatic melanoma (MEL) with BRAF V600E or V600K mutation, as detected by an FDA-approved test. [source]
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Vemurafenib in Melanoma (MEL) The U.S. Food and Drug Administration (FDA) granted regular approval to vemurafenib for the treatment of patients with unresectable or metastatic melanoma (MEL) with BRAF V600E mutation, as detected by an FDA-approved test. [source]
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Dabrafenib + Trametinib in Melanoma (MEL) The U.S. Food and Drug Administration (FDA) granted approval to dabrafenib in combination with trametinib for the adjuvant treament of patients with unresectable or metastatic melanoma (MEL) with BRAF V600E or V600K mutation, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection. [source]
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Dabrafenib + Trametinib in Non-Small Cell Lung Cancer (NSCLC) The U.S. Food and Drug Administration (FDA) granted approval to dabrafenib in combination with trametinib for the treament of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E, as detected by an FDA-approved test. [source]
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Dabrafenib in Melanoma (MEL) The U.S. Food and Drug Administration (FDA) granted approval to dabrafenib as a single agent for the treament of patients with unresectable or metastatic melanoma (MEL) with BRAF V600E mutation, as detected by an FDA-approved test. [source]
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Trametinib in Melanoma (MEL) The U.S. Food and Drug Administration (FDA) granted approval to trametinib as a single agent for the treament of patients with unresectable or metastatic melanoma (MEL) with BRAF V600E or V600K mutation, as detected by an FDA-approved test. [source]
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Vemurafenib in Melanoma (MEL) The U.S. Food and Drug Administration (FDA) granted regular approval to vemurafenib for the treatment of patients with unresectable or metastatic melanoma (MEL) with BRAF V600E mutation, as detected by an FDA-approved test. [source]
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Dabrafenib + Trametinib in Melanoma (MEL) The U.S. Food and Drug Administration (FDA) granted approval to dabrafenib in combination with trametinib for the adjuvant treament of patients with unresectable or metastatic melanoma (MEL) with BRAF V600E or V600K mutation, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection. [source]
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Dabrafenib + Trametinib in Non-Small Cell Lung Cancer (NSCLC) The U.S. Food and Drug Administration (FDA) granted approval to dabrafenib in combination with trametinib for the treament of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E, as detected by an FDA-approved test. [source]
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Dabrafenib in Melanoma (MEL) The U.S. Food and Drug Administration (FDA) granted approval to dabrafenib as a single agent for the treament of patients with unresectable or metastatic melanoma (MEL) with BRAF V600E mutation, as detected by an FDA-approved test. [source]
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Trametinib in Melanoma (MEL) The U.S. Food and Drug Administration (FDA) granted approval to trametinib as a single agent for the treament of patients with unresectable or metastatic melanoma (MEL) with BRAF V600E or V600K mutation, as detected by an FDA-approved test. [source]
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Vemurafenib in Melanoma (MEL) The U.S. Food and Drug Administration (FDA) granted regular approval to vemurafenib for the treatment of patients with unresectable or metastatic melanoma (MEL) with BRAF V600E mutation, as detected by an FDA-approved test. [source]
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Dabrafenib + Trametinib in Melanoma (MEL) The U.S. Food and Drug Administration (FDA) granted approval to dabrafenib in combination with trametinib for the adjuvant treament of patients with unresectable or metastatic melanoma (MEL) with BRAF V600E or V600K mutation, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection. [source]
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Dabrafenib + Trametinib in Non-Small Cell Lung Cancer (NSCLC) The U.S. Food and Drug Administration (FDA) granted approval to dabrafenib in combination with trametinib for the treament of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E, as detected by an FDA-approved test. [source]
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Dabrafenib in Melanoma (MEL) The U.S. Food and Drug Administration (FDA) granted approval to dabrafenib as a single agent for the treament of patients with unresectable or metastatic melanoma (MEL) with BRAF V600E mutation, as detected by an FDA-approved test. [source]
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Trametinib in Melanoma (MEL) The U.S. Food and Drug Administration (FDA) granted approval to trametinib as a single agent for the treament of patients with unresectable or metastatic melanoma (MEL) with BRAF V600E or V600K mutation, as detected by an FDA-approved test. [source]
BRAF p.V600E (Missense) FDA-Approved	Sensitivity to Vemurafenib in Melanoma (MEL) The U.S. Food and Drug Administration (FDA) granted regular approval to vemurafenib for the treatment of patients with unresectable or metastatic melanoma (MEL) with BRAF V600E mutation, as detected by an FDA-approved test. [source]

[More details]

Somatic Variant

BRAF p.V600E (Missense)

Dabrafenib + Trametinib
The U.S. Food and Drug Administration (FDA) granted approval to dabrafenib in combination with trametinib for the treament of patients with unresectable or metastatic melanoma (MEL) with BRAF V600E or V600K mutation, as detected by an FDA-approved test. [source]

Dabrafenib
Trametinib

Cell lines from the Sanger Institute's Genomics of Drug Discovery in Cancer (GDSC) are stratified by wild type and mutant status for the following molecular features. We then compare the drug response to the recommend therapy (or therapies) based on data from the GDSC.

Feature	N WT tested	N Mut tested	MWW statistic	MWW p-value
BRAF	621	136	58428.0	2.322e-12
BRAF Somatic Variant	659	98	49130.0	7.627e-17
BRAF Somatic Variant Missense	668	89	45390.0	6.330e-16
BRAF Somatic Variant Missense p.V600E	708	49	31960.0	5.518e-23

Feature	N WT tested	N Mut tested	MWW statistic	MWW p-value
BRAF	634	137	57546.5	2.344e-09
BRAF Somatic Variant	672	99	48043.5	9.083e-13
BRAF Somatic Variant Missense	681	90	45139.0	2.900e-13
BRAF Somatic Variant Missense p.V600E	721	50	29698.0	1.793e-14

[Preclinical evidence]

FDA-Approved
Investigate Actionability - High

The following assertion was the strongest match to the observed molecular feature.

Evidence:	FDA-Approved
Molecular feature:	MSI-High
Assertion:	Sensitivity to Pembrolizumab in Any solid tumor

The U.S. Food and Drug Administration (FDA) granted accelerated approval to pembrolizumab for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options. [source]

The following assertions are equivalent matches within this patient's ontology or stronger in another cancer type.

Molecular feature & evidence	Assertion & rationale
MSI-High FDA-Approved	Sensitivity to Pembrolizumab in Colorectal Adenocarcinoma (COADREAD) The U.S. Food and Drug Administration (FDA) granted accelerated approval to pembrolizumab for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. [source]

[More details]

Microsatellite Stability

MSI-High

Pembrolizumab
The U.S. Food and Drug Administration (FDA) granted accelerated approval to pembrolizumab for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options. [source]

FDA-Approved
Investigate Actionability - Low

The following assertion was the strongest match to the observed molecular feature.

Evidence:	FDA-Approved
Molecular feature:	BRCA2
Assertion:	Sensitivity to Talazoparib in Invasive Breast Carcinoma (BRCA)

The U.S. Food and Drug Administration (FDA) granted approval for talazoparib indicated for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated HER2-negative localy advanced or metastatic breast cancer. [source]

The following assertions are equivalent matches within this patient's ontology or stronger in another cancer type.

Molecular feature & evidence	Assertion & rationale
BRCA2 FDA-Approved	Sensitivity to Olaparib in Invasive Breast Carcinoma (BRCA) The U.S. Food and Drug Administration (FDA) granted approval for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2-negative metastatic breast cancer who have been treated with chemotherapy either in the neoadjuvant, adjuvant, or metastatic setting. [source]
BRCA2 FDA-Approved	Sensitivity to Olaparib in Ovarian Epithelial Tumor (OVT) The U.S. Food and Drug Administration (FDA) granted approval for olaparib for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. [source]
BRCA2 FDA-Approved	Sensitivity to Olaparib in High-Grade Serous Fallopian Tube Cancer (HGSFT) The U.S. Food and Drug Administration (FDA) granted approval for olaparib for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. [source]
BRCA2 FDA-Approved	Sensitivity to Olaparib in Peritoneal Serous Carcinoma (PSEC) The U.S. Food and Drug Administration (FDA) granted approval for olaparib for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. [source]
BRCA2 FDA-Approved	Sensitivity to Olaparib in Invasive Breast Carcinoma (BRCA) The U.S. Food and Drug Administration (FDA) granted approval for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2-negative metastatic breast cancer who have been treated with chemotherapy either in the neoadjuvant, adjuvant, or metastatic setting. [source]
BRCA2 FDA-Approved	Sensitivity to Olaparib in Ovarian Epithelial Tumor (OVT) The U.S. Food and Drug Administration (FDA) granted approval for olaparib for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. [source]
BRCA2 FDA-Approved	Sensitivity to Olaparib in High-Grade Serous Fallopian Tube Cancer (HGSFT) The U.S. Food and Drug Administration (FDA) granted approval for olaparib for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. [source]
BRCA2 FDA-Approved	Sensitivity to Olaparib in Peritoneal Serous Carcinoma (PSEC) The U.S. Food and Drug Administration (FDA) granted approval for olaparib for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. [source]
BRCA2 FDA-Approved	Sensitivity to Olaparib in Invasive Breast Carcinoma (BRCA) The U.S. Food and Drug Administration (FDA) granted approval for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2-negative metastatic breast cancer who have been treated with chemotherapy either in the neoadjuvant, adjuvant, or metastatic setting. [source]
BRCA2 FDA-Approved	Sensitivity to Olaparib in Ovarian Epithelial Tumor (OVT) The U.S. Food and Drug Administration (FDA) granted approval for olaparib for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. [source]
BRCA2 FDA-Approved	Sensitivity to Olaparib in High-Grade Serous Fallopian Tube Cancer (HGSFT) The U.S. Food and Drug Administration (FDA) granted approval for olaparib for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. [source]
BRCA2 FDA-Approved	Sensitivity to Olaparib in Peritoneal Serous Carcinoma (PSEC) The U.S. Food and Drug Administration (FDA) granted approval for olaparib for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. [source]
BRCA2 FDA-Approved	Sensitivity to Olaparib in Invasive Breast Carcinoma (BRCA) The U.S. Food and Drug Administration (FDA) granted approval for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2-negative metastatic breast cancer who have been treated with chemotherapy either in the neoadjuvant, adjuvant, or metastatic setting. [source]
BRCA2 FDA-Approved	Sensitivity to Olaparib in Ovarian Epithelial Tumor (OVT) The U.S. Food and Drug Administration (FDA) granted approval for olaparib for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. [source]
BRCA2 FDA-Approved	Sensitivity to Olaparib in High-Grade Serous Fallopian Tube Cancer (HGSFT) The U.S. Food and Drug Administration (FDA) granted approval for olaparib for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. [source]
BRCA2 FDA-Approved	Sensitivity to Olaparib in Peritoneal Serous Carcinoma (PSEC) The U.S. Food and Drug Administration (FDA) granted approval for olaparib for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. [source]

[More details]

Germline Variant

BRCA2 p.S1982fs (Frameshift)

Talazoparib
The U.S. Food and Drug Administration (FDA) granted approval for talazoparib indicated for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated HER2-negative localy advanced or metastatic breast cancer. [source]

Guideline
Investigate Actionability - High
[More details]

Rearrangement

COL1A1--CITED4 Fusion

Imatinib
Imatinib has shown clinical activity against localized and metastatic DFSP tumors containing t(17;22)(q22;q13). [source]

Imatinib

Feature	N WT tested	N Mut tested	MWW statistic	MWW p-value
COL1A1	370	37	6702.0	0.835
CITED4	386	21	3163.5	0.09
COL1A1 Fusions	407	0
CITED4 Fusions	407	0
COL1A1--CITED4	407	0

[Preclinical evidence]

Clinical evidence
Investigate Actionability - Low
[More details]

Somatic Variant

MSH2 p.D887N (Missense)

Pembrolizumab
Patients with defects in DNA mismatch repair genes may have enhanced sensitivity to immune checkpoint blockade. [source]

Variants and Features associated with Therapeutic Resistance

Predictive Implication

Feature Type

Feature

Therapy & Rationale

Guideline
Putatively Actionable

The following assertion was the strongest match to the observed molecular feature.

Evidence:	Guideline
Molecular feature:	BRAF p.V600E (Missense)
Assertion:	Resistance to Panitumumab in Colorectal Adenocarcinoma (COADREAD)

BRAF V600E makes response to panitumumab or cetuximab highly unlikely unless given with a BRAF inhibitor in metastatic colorectal cancer. [source]

The following assertions are equivalent matches within this patient's ontology or stronger in another cancer type.

Molecular feature & evidence	Assertion & rationale
BRAF p.V600E (Missense) Guideline	Resistance to Cetuximab in Colorectal Adenocarcinoma (COADREAD) BRAF V600E makes response to panitumumab or cetuximab highly unlikely unless given with a BRAF inhibitor in metastatic colorectal cancer. [source]
BRAF p.V600E (Missense) Guideline	Resistance to Cetuximab in Colorectal Adenocarcinoma (COADREAD) BRAF V600E makes response to panitumumab or cetuximab highly unlikely unless given with a BRAF inhibitor in metastatic colorectal cancer. [source]
BRAF p.V600E (Missense) Guideline	Resistance to Cetuximab in Colorectal Adenocarcinoma (COADREAD) BRAF V600E makes response to panitumumab or cetuximab highly unlikely unless given with a BRAF inhibitor in metastatic colorectal cancer. [source]
BRAF p.V600E (Missense) Guideline	Resistance to Cetuximab in Colorectal Adenocarcinoma (COADREAD) BRAF V600E makes response to panitumumab or cetuximab highly unlikely unless given with a BRAF inhibitor in metastatic colorectal cancer. [source]

[More details]

Somatic Variant

BRAF p.V600E (Missense)

Panitumumab
BRAF V600E makes response to panitumumab or cetuximab highly unlikely unless given with a BRAF inhibitor in metastatic colorectal cancer. [source]

Guideline
Investigate Actionability - High
[More details]

Microsatellite Stability

MSI-High

5-Fluorouracil
Patients with MSI-High colorectal cancer appear not to benefit from, and may be resistant to, 5-fluorouracil therapy. [source]

Variants and Features associated with Prognostic Information

Predictive Implication

Feature Type

Feature

Therapy & Rationale

Guideline
Putatively Actionable

The following assertion was the strongest match to the observed molecular feature.

Evidence:	Guideline
Molecular feature:	BRAF p.V600E (Missense)
Assertion:	Not favorable prognosis in Colorectal Adenocarcinoma

BRAF V600E alterations are associated with an unfavorable prognosis in MSI-low and microsatellite-stable patients. [source]

The following assertions are equivalent matches within this patient's ontology or stronger in another cancer type.

Molecular feature & evidence	Assertion & rationale
BRAF p.V600E (Missense) Guideline	Not favorable prognosis in Colorectal Adenocarcinoma (COADREAD) BRAF V600E alterations are associated with an unfavorable prognosis in MSI-low and microsatellite-stable patients. [source]
BRAF p.V600E (Missense) Guideline	Not favorable prognosis in Colorectal Adenocarcinoma (COADREAD) BRAF V600E alterations are associated with an unfavorable prognosis in MSI-low and microsatellite-stable patients. [source]
BRAF p.V600E (Missense) Guideline	Not favorable prognosis in Colorectal Adenocarcinoma (COADREAD) BRAF V600E alterations are associated with an unfavorable prognosis in MSI-low and microsatellite-stable patients. [source]
BRAF p.V600E (Missense) Guideline	Not favorable prognosis in Colorectal Adenocarcinoma (COADREAD) BRAF V600E alterations are associated with an unfavorable prognosis in MSI-low and microsatellite-stable patients. [source]

[More details]

Somatic Variant

BRAF p.V600E (Missense)

Not favorable
BRAF V600E alterations are associated with an unfavorable prognosis in MSI-low and microsatellite-stable patients. [source]

Guideline
Investigate Actionability - High
[More details]

Microsatellite Stability

MSI-High

Favorable
Patients with MSI-High colorectal cancer often have a favorable prognosis. [source]

Clinical evidence
Investigate Actionability - Low

The following assertion was the strongest match to the observed molecular feature.

Evidence:	Clinical evidence
Molecular feature:	ZRSR2 (Nonsense)
Assertion:	Not favorable prognosis in Myelodysplasia

NCCN guideline for Myelodysplastic Syndromes. [source]

The following assertions are equivalent matches within this patient's ontology or stronger in another cancer type.

Molecular feature & evidence	Assertion & rationale
ZRSR2 (Frameshift) Clinical evidence	Not favorable prognosis in Myelodysplasia (MDS) NCCN guideline for Myelodysplastic Syndromes. [source]
ZRSR2 (Frameshift) Clinical evidence	Not favorable prognosis in Myelodysplasia (MDS) NCCN guideline for Myelodysplastic Syndromes. [source]
ZRSR2 (Frameshift) Clinical evidence	Not favorable prognosis in Myelodysplasia (MDS) NCCN guideline for Myelodysplastic Syndromes. [source]
ZRSR2 (Frameshift) Clinical evidence	Not favorable prognosis in Myelodysplasia (MDS) NCCN guideline for Myelodysplastic Syndromes. [source]

[More details]

Somatic Variant

ZRSR2 p.N261I (Missense)

Not favorable
NCCN guideline for Myelodysplastic Syndromes. [source]

Clinical evidence
Investigate Actionability - Low

The following assertion was the strongest match to the observed molecular feature.

Evidence:	Clinical evidence
Molecular feature:	STAG2 (Nonsense)
Assertion:	Not favorable prognosis in Myelodysplasia

NCCN guideline for Myelodysplastic Syndromes. [source]

The following assertions are equivalent matches within this patient's ontology or stronger in another cancer type.

Molecular feature & evidence	Assertion & rationale
STAG2 (Frameshift) Clinical evidence	Not favorable prognosis in Myelodysplasia (MDS) NCCN guideline for Myelodysplastic Syndromes. [source]
STAG2 (Splice Site) Clinical evidence	Not favorable prognosis in Myelodysplasia (MDS) NCCN guideline for Myelodysplastic Syndromes. [source]
STAG2 (Frameshift) Clinical evidence	Not favorable prognosis in Myelodysplasia (MDS) NCCN guideline for Myelodysplastic Syndromes. [source]
STAG2 (Splice Site) Clinical evidence	Not favorable prognosis in Myelodysplasia (MDS) NCCN guideline for Myelodysplastic Syndromes. [source]
STAG2 (Frameshift) Clinical evidence	Not favorable prognosis in Myelodysplasia (MDS) NCCN guideline for Myelodysplastic Syndromes. [source]
STAG2 (Splice Site) Clinical evidence	Not favorable prognosis in Myelodysplasia (MDS) NCCN guideline for Myelodysplastic Syndromes. [source]
STAG2 (Frameshift) Clinical evidence	Not favorable prognosis in Myelodysplasia (MDS) NCCN guideline for Myelodysplastic Syndromes. [source]
STAG2 (Splice Site) Clinical evidence	Not favorable prognosis in Myelodysplasia (MDS) NCCN guideline for Myelodysplastic Syndromes. [source]

[More details]

Somatic Variant

STAG2 p.F467I (Missense)

Not favorable
NCCN guideline for Myelodysplastic Syndromes. [source]

Inferential
Investigate Actionability - High
[More details]

Aneuploidy

Not favorable
WGD was associated with adverse survival pan-cancer in patients with advanced disease and in cancers with heterogeneous clinical outcomes, even following the development of metastasis. [source]

Variants and Features that may be Biologically Relevant

Feature Type	Features
Copy Number	BLM Amplification, CTNNB1 Amplification, ERRFI1 Deletion, EWSR1 Amplification, JAK1 Deletion, TSC2 Deletion
Germline Variant	BRAF p.R509* (Nonsense)
Microsatellite Stability	Supporting variants: JAK1 Deletion, PRDM2 p.E282del (Deletion)
Mutational Signature	COSMIC Signature 7 (64%)
Somatic Variant	NTRK2 p.H300Y (Missense), PDGFRB p.G674E (Missense)

Comparison of molecular profile to cancer cell lines

The Molecular Oncology Almanac compares the somatic variants, copy number alterations, and rearrangements present in this tumor
to identify similar cell lines and their corresponding therapeutic sensitivities to aid in treatment hypothesis generation.

The 5 most similar cancer cell lines, of 452 tested

Cell line name (CCLE)

Sensitive therapies

Clinically relevant features

SKHEP1_LIVER

Aliases: ACH-000361 (Broad/DepMap), SIDM01110 (Sanger)

Sensitive to: AGI-5198, SN-38

Clinically relevant features: BRAF p.V600E, CDKN2A Deletion, CDKN2B Deletion, ERCC2 Missense, SMARCA4 Nonsense

Below lists somatic variants, copy number alterations, or fusions that appear in a Molecular Oncology Almanac, Cancer Hotspot, or Cancer Gene Census gene as well as the top 10 sensitive therapies that were tested against the cell line in GDSC1/GDSC2.

Somatic variants:

BRAF p.V600E, ERCC2 p.M724T, LEPROTL1 p.D57E, NF2 p.I264V, SMARCA4 p.E1582*

Copy number alterations:

BCR Deletion, BLM Deletion, CDKN2A Deletion, CDKN2B Deletion, IRF4 Amplification, MUC4 Amplification, PTPRD Deletion

Fusions: (None observed)

Therapeutic sensitivity (10 most sensitive):

Dataset	therapy	ln(ic50)	AUC	z score
GDSC2	AGI-5198	2.295597	0.885606	-2.810423
GDSC1	SN-38	-9.38477	0.052603	-2.256093
GDSC1	Doxorubicin	-4.127894	0.094794	-1.746938
GDSC1	NSC-207895	1.716658	0.73632	-1.570315
GDSC2	Nilotinib	0.918093	0.901523	-1.535689
GDSC1	Tipifarnib	-0.860009	0.359995	-1.491999
GDSC1	Etoposide	-1.208063	0.305949	-1.420639
GDSC1	DMOG	4.415167	0.321503	-1.369969
GDSC1	Veliparib	2.803374	0.962661	-1.303758
GDSC1	Bleomycin (10 uM)	-0.452696	0.502855	-1.264271

[More details]

AGI-5198, SN-38

BRAF p.V600E, CDKN2A Deletion, CDKN2B Deletion, ERCC2 Missense, SMARCA4 Nonsense

G361_SKIN

Aliases: ACH-000572 (Broad/DepMap), SIDM00857 (Sanger)

Sensitive to: Bexarotene, Bryostatin 1, Dabrafenib, Refametinib

Clinically relevant features: ALK Missense, ALK Missense, BRAF Amplification, BRAF p.V600E, CDKN2A Deletion, EGFR Amplification, MET Amplification

Somatic variants:

ALK p.G385S, ALK p.G689R, AMER1 p.R641*, BRAF p.V600E, CBLB p.F814S, CD79A p.E148G, CNTNAP2 p.P739S, CTNNA2 p.VRKQG96fs, MUC16 p.G9315V, MUC4 p.S534F, MUC4 p.V1571G, SPECC1 p.P907F, SPECC1 p.P907L, SPECC1 p.P907S, STK11 p.G279fs

Copy number alterations:

AKAP9 Amplification, ALK Deletion, BRAF Amplification, CARD11 Amplification, CDK6 Amplification, CDKN2A Deletion, CNOT3 Deletion, CNTNAP2 Amplification, CREB3L2 Amplification, CUX1 Amplification, EGFR Amplification, ELN Amplification, ETV1 Amplification, EZH2 Amplification, FAM131B Amplification, FKBP9 Amplification, GRM3 Amplification, GTF2I Amplification, HGF Amplification, HIP1 Amplification, HNRNPA2B1 Amplification, HOXA11 Amplification, HOXA13 Amplification, HOXA9 Amplification, IKZF1 Amplification, JAZF1 Amplification, KIAA1549 Amplification, LRP1B Deletion, MET Amplification, MNX1 Amplification, PDE4DIP Amplification, PMS2 Amplification, POT1 Amplification, RAC1 Amplification, RHEB Amplification, SBDS Amplification, SFRP4 Amplification, SMARCA4 Deletion, SMO Amplification, SND1 Amplification, TFPT Deletion, TRIM24 Amplification, TRRAP Amplification, ZBTB16 Deletion, ZNF479 Amplification

Fusions:

ACVR1--CYTIP

Therapeutic sensitivity (10 most sensitive):

Dataset	therapy	ln(ic50)	AUC	z score
GDSC2	Dabrafenib	-0.723223	0.555257	-2.224162
GDSC1	Bryostatin 1	-4.786909	0.887407	-2.159514
GDSC1	Bexarotene	1.265355	0.795426	-2.032625
GDSC1	Refametinib	-2.043773	0.358708	-2.00163
GDSC2	PLX-4720	1.120111	0.775351	-1.999236
GDSC1	rTRAIL	-3.4634	0.749522	-1.896197
GDSC2	Tamoxifen	1.791094	0.839701	-1.882421
GDSC1	QS11	0.706533	0.683033	-1.850396
GDSC2	Obatoclax Mesylate	-0.627835	0.567506	-1.81257
GDSC1	PAC-1	0.163003	0.800072	-1.675067

[More details]

Bexarotene, Bryostatin 1, Dabrafenib, Refametinib

ALK Missense, ALK Missense, BRAF Amplification, BRAF p.V600E, CDKN2A Deletion, EGFR Amplification, MET Amplification

IGR37_SKIN

Aliases: ACH-000650 (Broad/DepMap), SIDM01066 (Sanger)

Sensitive to: (5Z)-7-Oxozeaenol, CI-1040, Dabrafenib, ERK_2440, ERK_6604, PD0325901, PLX-4720, RAF_9304, Refametinib, Refametinib, SB52334, SB590885, Selisistat, Selumetinib, Trametinib

Clinically relevant features: AURKB Deletion, BRAF p.V600E, MLH3 somatic variant, TP53 Deletion, TP53 Frameshift

Somatic variants:

AKAP9 p.Y3128N, AURKB p.F88L, BRAF p.V600E, COL3A1 p.P895S, CSMD3 p.C2078S, DCC p.E2K, DIS3 p.P770S, EPAS1 p.P673S, ERC1 p.H721Q, ITK p.H121Y, KTN1 p.K141fs, LRP1B p.D61N, MEN1 p.D210E, MLH3 p.R1232S, MLLT1 p.S369F, MUC16 p.G4350R, MUC16 p.P700L, MUC16 p.R13398C, PAX7 p.K175N, PTPRD p.R561Q, RGPD3 p.E938K, TP53 p.C229fs

Copy number alterations:

AKT1 Deletion, ANKRD11 Deletion, AURKB Deletion, BCL11B Deletion, CBFA2T3 Deletion, DICER1 Deletion, FANCA Deletion, FGFR3 Deletion, FLCN Deletion, FSTL3 Deletion, GAS7 Deletion, GATA3 Deletion, GOLGA5 Deletion, GPS2 Deletion, HSP90AA1 Deletion, KLF6 Deletion, LARP4B Deletion, MAF Deletion, MAP2K4 Deletion, MC1R Deletion, MITF Amplification, N4BP2 Deletion, NCOR1 Deletion, NCOR2 Deletion, PER1 Deletion, PHOX2B Deletion, PLAG1 Amplification, PRPF8 Deletion, PTCH1 Amplification, RABEP1 Deletion, RFWD3 Deletion, RHOH Deletion, STK11 Deletion, TACC3 Deletion, TCL1A Deletion, TMPRSS2 Deletion, TP53 Deletion, TRIP11 Deletion, USP6 Deletion, WHSC1 Deletion, YWHAE Deletion, ZFHX3 Deletion

Fusions: (None observed)

Therapeutic sensitivity (10 most sensitive):

Dataset	therapy	ln(ic50)	AUC	z score
GDSC1	SB590885	-2.46916	0.293122	-4.75578
GDSC1	Selisistat	2.49932	0.835077	-4.446638
GDSC1	(5Z)-7-Oxozeaenol	-4.632813	0.032905	-3.569748
GDSC2	Dabrafenib	-3.36223	0.216522	-3.390736
GDSC1	RAF_9304	-2.425218	0.203482	-3.337126
GDSC1	Refametinib	-3.763	0.130697	-3.018654
GDSC2	PLX-4720	-0.444047	0.595468	-2.982493
GDSC1	SB52334	0.439094	0.535281	-2.963945
GDSC1	Refametinib	-3.79142	0.127929	-2.954985
GDSC2	ERK_6604	-1.500489	0.454987	-2.838606

[More details]

(5Z)-7-Oxozeaenol, CI-1040, Dabrafenib, ERK_2440, ERK_6604, PD0325901, PLX-4720, RAF_9304, Refametinib, Refametinib, SB52334, SB590885, Selisistat, Selumetinib, Trametinib

AURKB Deletion, BRAF p.V600E, MLH3 somatic variant, TP53 Deletion, TP53 Frameshift

DU4475_BREAST

Aliases: ACH-000258 (Broad/DepMap), SIDM01001 (Sanger)

Sensitive to: ABT737, AS605240, AZ628, Ara-G, CI-1040, Dabrafenib, ERK_2440, ERK_6604, Entinostat, GSK1904529A, KIN001-236, LIMK1 inhibitor BMS4, LJI308, LY2109761, Mitoxantrone, Nutlin-3a (-), PD0325901, PLX-4720, Pevonedistat, Phenformin, Pilaralisib, RAF_9304, RO-3306, RU-SKI 43, Refametinib, Refametinib, SB590885, SCH772984, SL0101, SU11274, Selumetinib, Tozasertib, Trametinib, Ulixertinib, Ulixertinib, VX-11e, WEHI-539, XMD14-99

Clinically relevant features: AR Missense, BRAF p.V600E, RB1 Deletion, SF3B1 somatic variant, STAG2 somatic variant

Somatic variants:

APC p.E1577*, AR p.R386C, BRAF p.V600E, CBFA2T3 p.R366Q, FAM47C p.E908K, FAT3 p.P4227S, FAT3 p.T2170P, ITGAV p.I214M, KMT2C p.D553N, MLLT10 p.Q529R, MUC4 p.P2368fs, N4BP2 p.Q770fs, NCOA2 p.F1301V, NCOA4 p.L228R, NRG1 p.N75I, PDE4DIP p.I1498V, PDPK1 p.G334R, PPFIBP1 p.F529fs, SETD1B p.Q1402R, SF3B1 p.L215fs, STAG2 p.T368N, ZFHX3 p.A2398D

Copy number alterations:

ABL2 Amplification, AKT3 Amplification, ALK Deletion, APC Deletion, ARHGEF10 Deletion, ARNT Amplification, ATM Deletion, BCL9 Amplification, BMPR1A Deletion, CCNC Deletion, CCND2 Deletion, CDC73 Amplification, CLP1 Deletion, CTNND1 Deletion, CYLD Deletion, CYSLTR2 Deletion, DDR2 Amplification, DDX10 Deletion, ELF3 Amplification, ELK4 Amplification, EPHA7 Deletion, ERBB3 Amplification, FAM135B Deletion, FCGR2B Amplification, FCRL4 Amplification, FH Amplification, FHIT Deletion, FOXO3 Deletion, GPS2 Deletion, H3F3A Amplification, HERPUD1 Deletion, HIP1 Amplification, IL6ST Deletion, JAK2 Deletion, LCP1 Deletion, LMNA Amplification, MAP2K4 Deletion, MAP3K1 Deletion, MDM4 Amplification, MGA Deletion, MLLT11 Amplification, MN1 Deletion, MUC1 Amplification, NTRK1 Amplification, NUP93 Deletion, OLIG2 Deletion, PAFAH1B2 Deletion, PARP1 Amplification, PBX1 Amplification, POU2AF1 Deletion, PRCC Amplification, PRDM1 Deletion, PREX2 Deletion, PRRX1 Amplification, PTPRC Amplification, RB1 Deletion, RGS7 Amplification, RIT1 Amplification, RUNX1 Deletion, S100A7 Amplification, SDHC Amplification, SDHD Deletion, SLC45A3 Amplification, TPM3 Amplification, TPR Amplification, ZBTB16 Deletion

Fusions: (None observed)

Therapeutic sensitivity (10 most sensitive):

Dataset	therapy	ln(ic50)	AUC	z score
GDSC1	AS605240	-4.078578	0.019993	-4.75695
GDSC1	SB590885	-2.039153	0.35348	-4.41058
GDSC2	Dabrafenib	-5.068587	0.044143	-4.145031
GDSC1	LIMK1 inhibitor BMS4	1.572108	0.721492	-3.606703
GDSC2	WEHI-539	-2.973504	0.245948	-3.505726
GDSC2	PLX-4720	-0.930781	0.531389	-3.288462
GDSC2	SCH772984	-4.019831	0.203031	-3.243074
GDSC2	ERK_6604	-2.130329	0.362487	-3.227274
GDSC2	PD0325901	-5.839973	0.358221	-3.128407
GDSC2	ERK_2440	-2.616675	0.296127	-3.074093

[More details]

ABT737, AS605240, AZ628, Ara-G, CI-1040, Dabrafenib, ERK_2440, ERK_6604, Entinostat, GSK1904529A, KIN001-236, LIMK1 inhibitor BMS4, LJI308, LY2109761, Mitoxantrone, Nutlin-3a (-), PD0325901, PLX-4720, Pevonedistat, Phenformin, Pilaralisib, RAF_9304, RO-3306, RU-SKI 43, Refametinib, Refametinib, SB590885, SCH772984, SL0101, SU11274, Selumetinib, Tozasertib, Trametinib, Ulixertinib, Ulixertinib, VX-11e, WEHI-539, XMD14-99

AR Missense, BRAF p.V600E, RB1 Deletion, SF3B1 somatic variant, STAG2 somatic variant

SKMEL5_SKIN

Aliases: ACH-000730 (Broad/DepMap), SIDM00080 (Sanger)

Sensitive to: FH535, IAP_7638, SB590885, UNC0642

Clinically relevant features: BRAF p.V600E, CCND1 Amplification, CDKN2A Deletion, CDKN2B Deletion, PIK3CB somatic variant, SMARCA4 Frameshift, TET2 somatic variant

Somatic variants:

APC p.L407F, BCL11B p.E504K, BIRC6 p.D2349N, BMP5 p.P417L, BRAF p.V600E, BRD3 p.Q662*, CNBD1 p.E304K, DGCR8 p.K561fs, FNBP1 p.337_344PHQPPPPP>P, IRS2 p.P934A, KDR p.S633F, KMT2D p.E4939K, KNSTRN p.S24F, LRP1B p.E72K, MLLT3 p.R298fs, MLLT6 p.G919R, NIN p.P1969S, NTRK2 p.P185L, PAK7 p.K247R, PIK3CB p.R48Q, PML p.R670H, POT1 p.F566C, PRDM14 p.E361K, PTPRB p.D1752N, PTPRT p.G1035fs, PTPRT p.P485S, RANBP2 p.P2215A, RICTOR p.P1602L, SETD2 p.P228L, SMARCA4 p.F1052fs, TET2 p.S477F, TPR p.T1553fs, USP44 p.S548F, WHSC1 p.P36S

Copy number alterations:

ASPSCR1 Amplification, AXIN2 Amplification, CANT1 Amplification, CCND1 Amplification, CDH10 Amplification, CDKN2A Deletion, CDKN2B Deletion, DDX5 Amplification, GPC5 Deletion, H3F3B Amplification, INPPL1 Amplification, NUMA1 Amplification, PRKAR1A Amplification, PTCH1 Amplification, PTPRD Deletion, RNF213 Amplification, RPTOR Amplification, SEPT9 Amplification, SRSF2 Amplification

Fusions: (None observed)

Therapeutic sensitivity (10 most sensitive):

Dataset	therapy	ln(ic50)	AUC	z score
GDSC1	IAP_7638	-2.522011	0.223833	-4.29224
GDSC1	UNC0642	0.09192	0.907135	-2.481357
GDSC1	FH535	-0.802279	0.290811	-2.302486
GDSC1	SB590885	0.608066	0.743449	-2.285454
GDSC1	GSK1059615	-3.009578	0.114528	-1.902058
GDSC2	Obatoclax Mesylate	-0.531448	0.574621	-1.722739
GDSC1	Embelin	1.149381	0.566363	-1.718901
GDSC1	Lenalidomide	2.597514	0.918926	-1.552228
GDSC1	CI-1040	-0.083321	0.556309	-1.544637
GDSC1	(5Z)-7-Oxozeaenol	-1.608525	0.337809	-1.542728

[More details]

FH535, IAP_7638, SB590885, UNC0642

BRAF p.V600E, CCND1 Amplification, CDKN2A Deletion, CDKN2B Deletion, PIK3CB somatic variant, SMARCA4 Frameshift, TET2 somatic variant

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