Next-generation sequencing for genetic testing of familial colorectal cancer syndromes

摘要: Genetic screening in families with high risk to develop colorectal cancer (CRC) prevents incurable disease and permits personalized therapeutic follow-up strategies. The advancement of next-generation sequencing (NGS) technologies has revolutionized the throughput DNA sequencing. A series 16 probands for either familial adenomatous polyposis (FAP; 8 cases) or hereditary nonpolyposis (HNPCC; were investigated intragenic mutations five CRC syndromes-associated genes (APC, MUTYH, MLH1, MSH2, MSH6) applying both a custom multigene Ion AmpliSeq NGS panel conventional Sanger Fourteen pathogenic variants detected 13/16 FAP/HNPCC (81.3 %); one FAP proband presented two co-existing variants, APC MUTYH. Thirteen these 14 by Sanger, while MSH2 mutation (L280FfsX3) was identified only This is due limitation approach resolving sequences close within homopolymeric stretches DNA. To evaluate performance our we assessed its capability resolve corresponding 2225 reported COSMIC database APC, MSH6. Our resolves where 2108 (94.7 %) occur. remaining 117 reside inside proximity homopolymer stretches; 27 (1.2 %) are imprecisely software but can be resolved visual inspection region, 90 (4.0 %) blind spots. In summary, would miss 4 % (90/2225) that need small set reactions solved. multiplex advantage analyzing multiple samples simultaneously, requiring reduced number regions not adequately NGS. implementation approaches routine diagnostics cost-effective significantly reduces diagnostic turnaround times.