WEEKLY IMPORTANT NEWS FROM MEDSCAPE AND OTHER SOURCES
Παρασκευή, 6 Ιανουαρίου 2017
GENETICS OF COLORECTAL CANCER IN YOUNGER PATIENTS
In a study reported in JAMA Oncology, Pearlman et al found that 16% of patients with early-onset colorectal cancer had germline cancer susceptibility mutations, with a wide array of such mutations being identified.
The study involved 450 patients diagnosed with colorectal cancer at age < 50 years from 51 hospitals in the Ohio Colorectal Cancer Prevention Initiative from January 2013 to June 2016. Mismatch repair deficiency was assessed by microsatellite instability and/or immunohistochemistry, and germline DNA was assessed for 25 mutations by next-generation sequencing.
Prevalence and Types
Overall, 75 mutations were found in 72 patients (16%). A total of 48 (10.7%) had mismatch repair–deficient tumors, with 40 of them (83.3%) having at least 1 gene mutation. A total of 37 had Lynch syndrome, 13 with MLH1 (including 1 with constitutional MLH1 methylation), 16 with MSH2, 1 with MSH2/monoallelic MUTYH, 2 with MSH6, and 5 with PMS2. One patient had the APC c.3920T>A, p.I1307K mutation and a PMS2 variant. Nine patients had double somatic mismatch repair mutations, including two with germline biallelic MUTYH mutations and one with somatic MLH1 methylation.
A total of 402 patients (89.3%) had mismatch repair–proficient tumors, with 32 (8%) having at least 1 mutation. Of them, nine had mutations in high-penetrance colorectal cancer genes (APC in five, APC/PMS2in one, biallelic MUTYH in two, and SMAD4 in one). Mutations in high- or moderate-penetrance genes not typically associated with colorectal cancer were identified in 13 (ATM in 3, ATM/CHEK2 in 1, BRCA1 in 2, BRCA2 in 4, CDKN2A in 1, and PALB2 in 2). Mutations in low-penetrance colorectal cancer genes were found in 10 patients (APC c.3920T>A, p.I1307K in 3 and monoallelic MUTYH in 7).
The investigators noted that 24 of 72 patients (33.3%) who tested positive for mutations did not meet established genetic testing criteria for the gene with the mutation.
The investigators concluded: “Of 450 patients with early-onset [colorectal cancer], 72 (16%) had gene mutations. Given the high frequency and wide spectrum of mutations, genetic counseling and testing with a multigene panel could be considered for all patients with early-onset [colorectal cancer].”
The study was supported in part by the National Cancer Institute.