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Germline mutations are inherited and in every cell; somatic mutations arise in the tumour only.
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.
Showing the technology this term belongs to: Germline (hereditary) testing.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
For TNBC, which is diagnosed young and is the PARP inhibitor-eligible subtype, the guideline makes germline testing part of the diagnostic workup rather than a referral decision.
It identifies a way that a good test produces a wrong answer, and it names the fix. Any plasma repair-gene result used to decide on a PARP inhibitor should be run with a paired blood control, or an older man may be treated for a marrow clone rather than for his prostate cancer.
It established plasma profiling as a routine alternative to tissue for the BRCA question in advanced prostate cancer, with a sensible rule attached: if plasma finds nothing actionable, go back to tissue. It also documents at scale both the extra resistance information plasma gives and the clonal haematopoiesis noise that comes with it.
Everyone with HER2-negative early breast cancer that meets high-risk criteria should be offered germline BRCA testing, because a positive result now changes treatment: a year of olaparib after chemotherapy reduces relapse and death. It does not apply to low-risk tumours, HER2-positive disease, or somatic-only BRCA mutations.
It is the evidence that PALB2 and somatic BRCA2 belong in the PARP inhibitor conversation even though the olaparib label stops at germline BRCA.
People with Lynch syndrome should be offered daily aspirin, which roughly halves bowel cancer risk with a delayed and durable effect. Whether a lower dose (as tested in CAPP3) is as effective, and whether the finding extends to the general population, are separate questions.
It defines who a homologous recombination result should send to platinum: core-gene and biallelic carriers, germline or somatic, rather than any repair-gene variant.
The document that made biomarker testing part of routine pancreatic cancer care in the United States; the 2018 version it built on fixed the second-line chemotherapy sequence still used in most guidelines.
Shares Let clinics contact relatives directly when a cancer gene is found, Founder mutation (BRCA1 185delAG and 5382insC, BRCA2 6174delT), Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis and poor survival outcomes in prostate cancer, Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories.
Shares Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer, Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma, Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer, Association of clonal haematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference.
Shares Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis and poor survival outcomes in prostate cancer, Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories, Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer, Real-time genomic characterization of advanced pancreatic cancer to enable precision medicine.
Shares ClinVar, Mutation, Germline testing in patients with breast cancer: ASCO-Society of Surgical Oncology guideline, Association of clonal haematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference.
Shares Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer, 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, Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma, Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer.
Shares Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis and poor survival outcomes in prostate cancer, Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas, Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer, Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines.
Shares Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer, Association of clonal haematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference, Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines, Genomic analysis of circulating tumour DNA in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms.
Shares Germline testing in patients with breast cancer: ASCO-Society of Surgical Oncology guideline, Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer, Metastatic Pancreatic Cancer: ASCO Guideline Update, Homologous recombination deficiency (HRD) in breast cancer.