Somatic mutations in CDH1 and CTNNB1 in primary carcinomas at 13 anatomic sites
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Evan L. Busch1,2,3, Jason L. Hornick4, Renato Umeton5, Adem Albayrak5, Neal I. Lindeman4, Laura E. MacConaill4, Elizabeth P. Garcia4, Matthew Ducar4 and Timothy R. Rebbeck2,3
1Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
2Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
4Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
5Department of Informatics, Dana-Farber Cancer Institute, Boston, MA 02215, USA
Evan L. Busch, email: [email protected]
Keywords: metastasis, carcinomas, epithelial-mesenchymal transition, mutation, detachment
Received: June 27, 2017 Accepted: September 01, 2017 Published: September 21, 2017
Metastases are involved in most cancer deaths. Evidence has suggested that cancer cell detachment from primary tumors might occur largely via the mechanism of epithelial-mesenchymal transition (EMT) activated by epigenetic events, but data addressing other possible triggers of detachment, particularly genetic mutations, have been limited. Using the Profile study of cancer genomics at Dana-Farber Cancer Institute, we examined somatic mutations in the EMT genes CDH1 in 5,106 primary carcinomas and CTNNB1 in 7,578 primary carcinomas across 13 anatomic sites: urinary bladder, breast, colon/rectum, endometrium, esophagus, kidney, lung, ovary, pancreas, prostate, skin (non-melanoma), stomach, and thyroid. For each gene and anatomic site, we calculated the prevalence of primary carcinomas with at least one mutation. Across all anatomic sites, 4% of carcinomas had at least one CDH1 mutation and 4% of carcinomas had at least one CTNNB1 mutation. By anatomic site, the observed prevalence of carcinomas with at least one mutation was less than 5% at 10 sites for CDH1 and 12 sites for CTNNB1. Tumor stage data were available for a subset of breast, colorectal, lung, and prostate tumors. Among patients from this subset who were diagnosed with regional or distant disease, only 4% had a CDH1 mutation and 1% had a CTNNB1 mutation in the primary tumor. The low mutation prevalences, especially among those with diagnoses of regional or distant disease, suggest that somatic mutations in CDH1 and CTNNB1 are unlikely to explain a substantial proportion of cancer cell detachment from primary carcinomas originating at most anatomic sites.
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