domingo, 19 de agosto de 2018

Clinical genetic testing outcome with multi-gene panel in Asian patients with multiple primary cancers. - PubMed - NCBI

2018 Jul 17;9(55):30649-30660. doi: 10.18632/oncotarget.25769. eCollection 2018 Jul 17.

Clinical genetic testing outcome with multi-gene panel in Asian patients with multiple primary cancers.

Chan GHJ1, Ong PY1, Low JJH2, Kong HL1, Ow SGW1, Tan DSP1,3, Lim YW1, Lim SE1, Lee SC1,3.

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Abstract

BACKGROUND:

Developing multiple cancers is an indicator of underlying hereditary cancer predisposition, but there is a paucity of data regarding the clinical genetic testing outcomes of these patients.

METHODS:

We compared cancer index patients with ≥2 primary malignancies versus 1 primary cancer who underwent clinical evaluation and testing with multi-gene panels comprising up to 49 genes from 1998-2016.

RESULTS:

Among 1191 cancer index patients, 80.6%, 17.2%, and 2.2% respectively had 1, 2, and ≥3 primary malignancies. For patients with 2 primary cancers (n=205), the most common cancer pairs were bilateral breast (37.5%), breast-ovary (11.7%), endometrium-ovary (9.2%), colon-endometrium (3.9%) and colon-colon (3.4%). 42.3% patients underwent gene testing including 110/231 (47.6%) with multiple malignancies. Pathogenic variants were found more frequently in younger patients, in those with a family history of cancer related to the suspected syndrome, and a trend towards significance in those with multiple primary cancers (35.5% vs. 25.6%, p = 0.09). In patients with multiple cancers, pathogenic variants were most commonly identified in BRCA1 (38.5%), BRCA2 (17.9%), and the mismatch repair genes (20.5%), while 23.1% of pathogenic mutations were in other moderate- to high-penetrance cancer predisposition genes including APC, ATM, MUTYH, PALB2, RAD50 and TP53.

CONCLUSION:

Patients with multiple cancers were more likely to carry pathogenic mutations than those with single cancer. About three-quarters of deleterious mutations in patients with multiple primary cancers were in BRCA1/2 and the mismatch repair genes, but multi-gene panel testing facilitated the detection of mutations in another 6 genes and is warranted in this high-risk population.