Frequent PIK3CA Mutations in Colorectal and Endometrial Tumors With 2 or More Somatic Mutations in Mismatch Repair Genes
| Autor: | Emily H. Turner, Sheena M. Scroggins, Mallory Beightol, Paul J. Goodfellow, Christina Smith, Heather Hampel, Rachel Pearlman, Albert de la Chapelle, William M. Grady, Edward H. Lin, Mark Arnold, Jonathan F. Tait, Stacey A. Cohen, Colin C. Pritchard, David E. Cohn, Ted Gooley, Sigurdis Haraldsdottir, Stephen J. Salipante, Angela Jacobson |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Hepatology biology Somatic cell Gastroenterology Microsatellite instability medicine.disease medicine.disease_cause MLH1 digestive system diseases Germline Lynch syndrome 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Germline mutation 030220 oncology & carcinogenesis medicine Cancer research biology.protein PTEN KRAS neoplasms |
| Zdroj: | Gastroenterology. 151:440-447.e1 |
| ISSN: | 0016-5085 |
| Popis: | Background & Aims Some colorectal and endometrial tumors with microsatellite instability not attributable to MLH1 hypermethylation or germline mutations contain 2 or more somatic mutations in genes encoding mismatch repair (MMR) proteins. We sought to define the molecular phenotype of this newly recognized tumor subtype. Methods From 2 prospective studies of the efficacy of screening for Lynch syndrome, we identified patients with colorectal and endometrial tumors who had 2 or more somatic (but not germline) mutations in genes encoding MMR proteins (double somatic). We determined the frequencies of tumor mutations in PIK3CA , BRAF , KRAS , NRAS , and PTEN by targeted next-generation sequencing and used logistic-regression models to compare them with those from patients with Lynch syndrome, MLH1 -hypermethylated, or microsatellite-stable tumors. We validated our findings using independent data sets from The Cancer Genome Atlas. Results Among colorectal cancer cases, we found that 14 of 21 (67%) patients with double somatic tumors also had PIK3CA mutations, compared with 4 of 18 (22%) tumors from patients with Lynch syndrome, 2 of 10 (20%) tumors with MLH1 hypermethylation, and 12 of 78 (15%) tumors with microsatellite stability ( P PIK3CA were detected in all 13 patients with double somatic endometrial cancers ( P = .04 compared with other subgroups). We did not detect BRAF mutations in patients with double somatic colorectal tumors or Lynch syndrome. We found highly similar results in a validation cohort from The Cancer Genome Atlas (113 patients with colorectal tumors, 178 endometrial tumors); 100% of double somatic cases had a somatic mutation in PIK3CA ( P Conclusions Most patients with colorectal or endometrial tumors with 2 or more somatic (but not germline) mutations in MMR proteins also have mutations in PIK3CA ; mutations in PIK3CA are detected at substantially higher frequencies in these double somatic tumors than in other microsatellite-instability subgroups. PIK3CA mutation status might be used to identify a specific group of colorectal tumors, and to select treatment or determine prognosis. |
| Databáze: | OpenAIRE |
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