期刊
HUMAN PATHOLOGY
卷 71, 期 -, 页码 117-125出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.humpath.2017.10.014
关键词
Merkel cell carcinoma; SNP microarray; Copy number aberrations; Next-generation sequencing; TP53; RBI
类别
资金
- Nova Scotia Health Authority Research Fund
- DPLM Fund for Molecular Pathology housed at the QE II Foundation, Halifax, Nova Scotia, Canada
Tumorigenesis in Merkel cell carcinoma (MCC) is driven by (1) clonal integration of the Merkel cell polyomavirus (MCPyV) in neoplastic cells and/or (2) genetic damage by ultraviolet (UV) light. A higher mutational burden, a UV-mutational signature, and many mutations in the TP53 and RBI genes characterize the virus-negative subset. MCPyV-negative MCCs include combined (often squamous and neuroendocrine) and pure (neuroendocrine) tumors. Because a combined morphology could elude detection microscopically, we sought a genetic link between combined and pure virus-negative tumors. From a global cohort of 46 cases, 9 pure MCPyV-positive, 9 pure MCPyV-negative, and 10 combined MCPyV-negative MCCs were studied by genome-wide microarray in search of copy number aberrations. The entire cohort (n = 46) was evaluated by next-generation sequencing for mutations in selected tumor suppressor genes and oncogenes. More copy number aberrations and a greater fraction of the genome were changed in combined and pure MCPyV-negative tumors relative to MCPyV-positive cases (P < .01 for all comparisons). No difference in these parameters was found between the 2 MCPyV-negative groups. Copy number loss of RBI or an inactivating RBI mutation (either or both) was common in combined (8/10, 80%) and pure (7/9, 78%) MCPyV-negative tumors but not MCPyV-positive cases (1/9, 11%). A similar trend was seen for TP53 (combined [2/10, 20%] and pure virus-negative tumors [5/9, 56%] showed gene copy number loss or mutations contrasted with pure virus-positive cases [0/9, 0%]). The shared genetic profiles of combined and pure MCPyV-negative tumors link these subsets and separate them from MCPyV-positive tumors. (C) 2017 Elsevier Inc. All rights reserved.
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