# Germline vs somatic mutations

Source: https://onco.cc/terms/germline-vs-somatic/  
OnCo record `germline-vs-somatic` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Germline mutations are inherited and in every cell; somatic mutations arise in the tumour only.

## Summary

Germline mutations are inherited and present in every cell of the body, whereas somatic mutations arise only in the tumour. Germline changes in BRCA, the Lynch syndrome genes or TP53 in Li-Fraumeni syndrome shape cancer risk and affect family members, while somatic mutations are what drive the tumour itself. Tumour-only sequencing can fail to tell the two apart, so paired tumour-normal sequencing is preferred. The term is linked to Germline (hereditary) testing, Lynch syndrome and the ClinVar collection, and it is referenced by the Wilms tumour and Retinoblastoma entries, by Mary-Claire King and Angelina Jolie, by the bottleneck on unidentified inherited risk, and by ideas on reflex germline testing and population germline screening with cascade testing.

## Fields

- Kind: Term
- Last checked: 2026-09-04
- Also known as: germline; somatic; inherited mutations; tumour-normal

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Germline_mutation
- Wikipedia: https://en.wikipedia.org/wiki/Germline_mutation

## Connected records

- cancers: [Adrenocortical carcinoma](https://onco.cc/cancers/adrenocortical/), [Advanced and metastatic adrenocortical carcinoma (ENSAT stage IV or unresectable)](https://onco.cc/cancers/advanced-adrenocortical-carcinoma/), [BRCA or PALB2-mutant pancreatic ductal adenocarcinoma](https://onco.cc/cancers/brca-palb2-pdac/), [BRCA-associated triple-negative breast cancer](https://onco.cc/cancers/brca-associated-tnbc/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Familial adenomatous polyposis-associated colorectal cancer](https://onco.cc/cancers/fap-associated-colorectal-cancer/), [Localised adrenocortical carcinoma (ENSAT stage I to III, resectable)](https://onco.cc/cancers/localised-adrenocortical-carcinoma/), [Lynch syndrome-associated colorectal cancer](https://onco.cc/cancers/lynch-associated-colorectal-cancer/), [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma](https://onco.cc/cancers/msi-high-pdac/), [Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)](https://onco.cc/cancers/multiple-endocrine-neoplasia/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Retinoblastoma](https://onco.cc/cancers/retinoblastoma/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/), [Wilms tumour (nephroblastoma)](https://onco.cc/cancers/wilms-tumor/)
- technologies: [Aspirin for cancer prevention and adjuvant therapy](https://onco.cc/technologies/aspirin-cancer-prevention/), [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [Polygenic risk scores for cancer](https://onco.cc/technologies/polygenic-risk-scores/)
- key papers: [Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer](https://onco.cc/key-papers/paper-hu-germline-mutations-pancreatic-cancer-risk-jama-2018/), [Association of clonal haematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference](https://onco.cc/key-papers/paper-jensen-clonal-haematopoiesis-cfdna-interference-prostate-jama-oncol-2021/), [CAPP2: two years of aspirin cuts bowel cancer in Lynch syndrome by more than a third over 10 years](https://onco.cc/key-papers/paper-capp2-aspirin-lynch-lancet-2020/), [Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma](https://onco.cc/key-papers/paper-shindo-germline-sporadic-pancreatic-jco-2017/), [Genomic analysis of circulating tumour DNA in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms](https://onco.cc/key-papers/paper-tukachinsky-ctdna-3334-advanced-prostate-ccr-2021/), [Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection](https://onco.cc/key-papers/paper-park-hrd-pancreatic-platinum-ccr-2020/), [Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis and poor survival outcomes in prostate cancer](https://onco.cc/key-papers/paper-castro-germline-brca-prostate-outcomes-jco-2013/), [Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories](https://onco.cc/key-papers/paper-taylor-germline-brca2-evolutionary-trajectories-nat-commun-2017/), [Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer](https://onco.cc/key-papers/paper-yurgelun-germline-second-hits-resected-pancreatic-genet-med-2019/), [Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas](https://onco.cc/key-papers/paper-palles-germline-pole-pold1-proofreading-nat-genet-2013/), [Germline testing in patients with breast cancer: ASCO-Society of Surgical Oncology guideline](https://onco.cc/key-papers/paper-bedrosian-asco-sso-germline-testing-breast-jco-2024/), [Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1](https://onco.cc/key-papers/paper-ligtenberg-epcam-deletion-msh2-silencing-nat-genet-2009/), [Inherited DNA-repair gene mutations in men with metastatic prostate cancer](https://onco.cc/key-papers/paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016/), [Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer](https://onco.cc/key-papers/paper-couch-tnbc-germline-17-genes-jco-2015/), [Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer](https://onco.cc/key-papers/paper-isaacsson-velho-intraductal-germline-dna-repair-prostate-2018/), [Metastatic Pancreatic Cancer: ASCO Guideline Update](https://onco.cc/key-papers/paper-asco-metastatic-pancreatic-cancer-guideline-update-jco-2020/), [MSH2 loss in primary prostate cancer](https://onco.cc/key-papers/paper-guedes-msh2-loss-primary-prostate-ccr-2017/), [OlympiA: a year of olaparib after surgery for BRCA-mutated, high-risk early breast cancer](https://onco.cc/key-papers/paper-olympia-nejm-2021/), [PAOLA-1: olaparib added to bevacizumab maintenance in newly diagnosed ovarian cancer, with benefit confined to HRD-positive tumours](https://onco.cc/key-papers/paper-paola-1-nejm-2019/), [Phase II study of maintenance rucaparib in patients with platinum-sensitive advanced pancreatic cancer and a pathogenic germline or somatic variant in BRCA1, BRCA2, or PALB2](https://onco.cc/key-papers/paper-reiss-rucaparib-maintenance-brca-palb2-pancreatic-jco-2021/), [Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines](https://onco.cc/key-papers/paper-nicolosi-germline-variants-prostate-testing-guidelines-jama-oncol-2019/), [Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade](https://onco.cc/key-papers/paper-abida-msi-prostate-checkpoint-blockade-jama-oncol-2019/), [PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations](https://onco.cc/key-papers/paper-profound-nejm-2020/), [PROSE consortium: preventive surgery lowers cancer and death in BRCA1 and BRCA2 carriers](https://onco.cc/key-papers/paper-brca-risk-reducing-surgery-jama-2010/), [Real-time genomic characterization of advanced pancreatic cancer to enable precision medicine](https://onco.cc/key-papers/paper-aguirre-real-time-genomic-characterisation-pancreatic-cancer-discov-2018/), [SOLO-1: two years of olaparib maintenance after first-line chemotherapy for BRCA-mutated ovarian cancer](https://onco.cc/key-papers/paper-solo-1-nejm-2018/), [SU2C-PCF: integrative clinical genomics of advanced prostate cancer](https://onco.cc/key-papers/paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015/), [TRITON2: rucaparib in men with metastatic castration-resistant prostate cancer harbouring a BRCA1 or BRCA2 alteration](https://onco.cc/key-papers/paper-abida-triton2-rucaparib-brca-jco-2020/)
- terms: [Colibactin](https://onco.cc/terms/colibactin/), [Extended RAS testing](https://onco.cc/terms/extended-ras-testing/), [Familial pancreatic cancer and inherited risk (who qualifies for surveillance)](https://onco.cc/terms/familial-pancreatic-cancer/), [Founder mutation (BRCA1 185delAG and 5382insC, BRCA2 6174delT)](https://onco.cc/terms/founder-mutation/), [Germline BRCA mutation (gBRCA)](https://onco.cc/terms/gbrca-mutation/), [Germline BRCA testing criteria for triple-negative breast cancer (UK)](https://onco.cc/terms/germline-brca-testing-criteria-tnbc/), [Hereditary cancer syndromes](https://onco.cc/terms/hereditary-cancer-syndromes/), [Homologous recombination deficiency (HRD) in breast cancer](https://onco.cc/terms/hrd-in-breast-cancer/), [Li-Fraumeni syndrome (germline TP53)](https://onco.cc/terms/li-fraumeni/), [Lynch syndrome](https://onco.cc/terms/lynch-syndrome/), [Mutation](https://onco.cc/terms/mutation/), [R-spondin fusion](https://onco.cc/terms/rspo-fusion/), [Somatic mutation theory of cancer](https://onco.cc/terms/somatic-mutation-theory/), [Somatic mutations from exome and genome sequencing (WXS, WGS)](https://onco.cc/terms/somatic-mutations-wxs-wgs/), [Variant calling](https://onco.cc/terms/variant-calling/), [Von Hippel-Lindau disease](https://onco.cc/terms/vhl-disease/)
- roadmaps: [Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question](https://onco.cc/roadmaps/pancreatic-roadmap/)
- ideas: [Ancestry-aware pharmacology: drug-level sub-studies across populations before approval](https://onco.cc/ideas/idea-tr1-ancestry-aware-pharmacology-programme/), [Automatic germline testing for every cancer type where it changes care](https://onco.cc/ideas/idea-prev-reflex-germline-testing/), [Let clinics contact relatives directly when a cancer gene is found](https://onco.cc/ideas/idea-prev-cascade-direct-contact-relatives/), [Population germline screening for hereditary cancer genes with cascade testing](https://onco.cc/ideas/idea-moon-population-germline-screening/), [Surveillance for every germline carrier found by universal testing, inside a registry rather than a research exception](https://onco.cc/ideas/idea-pdac-surveillance-for-every-germline-carrier/), [Universal tumour and germline sequencing at diagnosis feeding a shared learning system](https://onco.cc/ideas/idea-moon-universal-sequencing-learning-system/)
- biomarkers: [Circulating tumour DNA fraction (and what a negative plasma result means)](https://onco.cc/biomarkers/ctdna-tumour-fraction/), [Germline BRCA1/2 pathogenic variant (gBRCAm)](https://onco.cc/biomarkers/brca-germline/), [Homologous recombination repair gene mutation in prostate cancer](https://onco.cc/biomarkers/hrr-gene-mutation/), [Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations](https://onco.cc/biomarkers/brca-somatic/)
- collections: [ClinVar](https://onco.cc/collections/clinvar/)
- people: [Angelina Jolie](https://onco.cc/people/angelina-jolie/), [Mary-Claire King](https://onco.cc/people/mary-claire-king/)
- bottlenecks: [Inherited risk is mostly unidentified](https://onco.cc/bottlenecks/b-hereditary-risk/)
- trials: [ALASCCA](https://onco.cc/trials/alascca/)
- institutions: [HUS Comprehensive Cancer Center, Helsinki University Hospital](https://onco.cc/institutions/helsinki-hus/)
- pathways: [Double-strand break repair: HR versus end joining](https://onco.cc/pathways/homologous-recombination-repair/), [Drivers, passengers & the two-hit model](https://onco.cc/pathways/oncogene-activation-two-hit/), [The p53 network (guardian of the genome)](https://onco.cc/pathways/p53-mdm2-axis/)
- drugs: [BRACAnalysis CDx](https://onco.cc/drugs/bracanalysis-cdx/), [Tempus xT CDx](https://onco.cc/drugs/tempus-xt-cdx/)

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