Carcinogenesis of squamous cell carcinomas (SCCs) in the anogenital tract and head and neck region is heterogeneous. A substantial proportion of SCC in the vulva, anus, and head and neck follows a human papillomavirus (HPV)-induced carcinogenic pathway. However, the molecular pathways of carcinogenesis in the HPV-independent lesions are not completely understood. We hypothesized that oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations might represent a carcinogenic mechanism in a proportion of those HPV-negative cancers. Considering the repeated observation of KRAS-associated p16(INK4a) overexpression in human tumors, it was assumed that KRAS mutations might be particularly present in the group of HPV-negative, p16(INK4a)-positive cancers. To test this hypothesis, we analyzed 66 anal, vulvar, and head and neck SCC with known immunohistochemical p16(INK4a) and HPV DNA status for KRAS mutations in exon 2 (codons 12, 13, and 15). We enriched the tumor collection with HPV DNA-negative, p16(INK4a)-positive cancers. A subset of 37 cancers was also analyzed for mutations in the B-Raf proto-oncogene, serine/threonine kinase (BRAF) gene. None of the 66 tumors harbored mutations in KRAS exon 2, thus excluding KRAS mutations as a common event in SCC of the anogenital and head and neck region and as a cause of p16(INK4a) expression in these tumors. In addition, no BRAF mutations were detected in the 37 analyzed tumors. Further studies are required to determine the molecular events underlying HPV-negative anal, vulvar, and head and neck carcinogenesis. Considering HPV-independent p16(INK4a) overexpression in some of these tumors, particular focus should be placed on alternative upstream activators and potential downstream disruption of the p16(INK4a) pathway. (C) 2014 Elsevier Inc. All rights reserved.
|Data di pubblicazione:||2014|
|Titolo:||No evidence of oncogenic KRAS mutations in squamous cell carcinomas of the anogenital tract and head and neck region independent of human papillomavirus and p16 (INK4a) status|
|Autore/i:||Prigge, Es; Urban, K; Stiegler, S; Muller, M; Kloor, M; Mai, S; Ottstadt, M; Lohr, F; Wenz, F; Wagner, S; Wittekindt, C; Klussmann, Jp; Hampl, M; Doeberitz, Mvk; Reuschenbach, M|
|Digital Object Identifier (DOI):||10.1016/j.humpath.2014.08.001|
|Codice identificativo ISI:||WOS:000343967300021|
|Codice identificativo Scopus:||2-s2.0-84908335846|
|Citazione:||No evidence of oncogenic KRAS mutations in squamous cell carcinomas of the anogenital tract and head and neck region independent of human papillomavirus and p16 (INK4a) status / Prigge, Es; Urban, K; Stiegler, S; Muller, M; Kloor, M; Mai, S; Ottstadt, M; Lohr, F; Wenz, F; Wagner, S; Wittekindt, C; Klussmann, Jp; Hampl, M; Doeberitz, Mvk; Reuschenbach, M. - In: HUMAN PATHOLOGY. - ISSN 0046-8177. - 45:11(2014), pp. 2347-2354.|
|Tipologia||Articolo su rivista|
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