Summary: This resource lists hereditary cancer genes in which variants detected on biomarker testing warrant genetic testing for inherited cancer risk according to ESMO recommendations.
By JAX Clinical Education | October 2025
Biomarker testing performed for treatment decision-making may identify variants that are also present in the germline, conferring inherited cancer risk to the patient and relatives. Additional genetic testing for inherited cancer risk may be indicated to provide the most accurate and complete information about potential germline variants.
The purpose of this resource is to list hereditary cancer genes that have published medical management recommendations and/or strong evidence supporting the association of the gene with cancer risk. The clinician should consider additional factors in the decision to refer for germline testing: the patient’s tumor type, age at diagnosis, personal and family history, variant allele fraction (VAF), test type (somatic only vs. paired germline/somatic) and the utility of genetic testing for inherited cancer risk for the specific individual.
This list is based on recommendations from the European Society for Medical Oncology (ESMO). This list is not specific to any biomarker test offering, is not exhaustive, and is likely to change over time.
Bold genes: Genetic testing for inherited cancer risk is generally recommended. Other genes: Consider genetic testing for inherited cancer risk based on patient age at diagnosis, tumor type, family history, and other factors.
APC | MSH6 | SDHB |
ATM | MUTYH* | SDHC |
BAP1 | NF1 | SDHD |
BARD1 | PALB2 | SMAD3 |
BRCA1 | PMS2 | SMAD4 |
BRCA2 | POLD1 | SMARCA4 |
BRIP1 | POLE | SMARCB1 |
CDH1 | PTCH1 | SUFU |
CDKN2A | PTEN | TP53 |
CHEK2 | RAD51C | TSC1 |
DICER1 | RAD51D | TSC2 |
FH | RB1 | VHL |
FLCN | RET | WT1 |
MLH1 | SDHA | |
MSH2 | SDHAF2 | |
* genetic testing for inherited cancer risk only recommended when two pathogenic/likely pathogenic variants are present in the gene | ||
Indications for Genetic Testing for Inherited Cancer Risk After Biomarker Testing. Provides a quick reference about the factors to consider when determining the appropriateness of genetic testing for inherited cancer risk.
Indications for Germline Testing After Genomic Tumor Testing. Practice identifying patients for germline referral based on test type, family history, and gene variant or biomarker.
Kuzbari Z, Bandlamudi C, Loveday C, et al. Germline-focused analysis of tumour-detected variants in 49,264 cancer patients: ESMO Precision Medicine Working Group recommendations. Ann Oncol. 2023;34(3):215-227. doi:10.1016/j.annonc.2022.12.003
Disclaimer
All information in this resource is provided for educational purposes only.