Mutations in genes encoding PI3K-AKT and MAPK signaling define anogenital papillary hidradenoma
Autor: | Hans-Peter Sinn, Albrecht Stenzinger, Jochen K. Lennerz, Nicole Pfarr, Christa Flechtenmacher, Kathrin Ridinger, K. Lorenz, Frederick Klauschen, Jan Budczies, Volker Endris, Roland Penzel, Wilko Weichert, Arne Warth, Michael Bockmayr, Moritz von Winterfeld |
---|---|
Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Sanger sequencing Cancer Research Mutation Hidradenoma Papillary hidradenoma Biology medicine.disease Bioinformatics medicine.disease_cause Malignant transformation Benign tumor 03 medical and health sciences symbols.namesake 030104 developmental biology 0302 clinical medicine Hyperplastic Polyp 030220 oncology & carcinogenesis Genetics medicine Cancer research symbols Gene |
Zdroj: | Genes, Chromosomes and Cancer. 55:113-119 |
ISSN: | 1045-2257 |
Popis: | Papillary hidradenoma (a.k.a. hidradenoma papilliferum) is a benign tumor of the anogenital region that almost exclusively arises in middle-aged Caucasian women. These tumors may recur and rare cases of malignant development have been reported. The genetic basis of papillary hidradenoma is currently unknown. Hence, we employed targeted high-coverage next generation sequencing interrogating 50 cancer-related genes and conventional Sanger sequencing to investigate the mutational landscape in a cohort of 15 cases. Additionally, we analyzed the HPV status of these tumors. Thirteen cases (87%) harbored mutations in cancer-related genes. Recurrent mutations in PIK3CA and AKT1 were present in 10 of the cases (67%). One PIK3CA mutated case had a concomitant STK11 mutation. Three cases harbored mutually exclusive mutations in BRAF, APC and ERBB4. The remaining two cases showed no mutations. None of the cases harbored DNA of human papilloma virus. Our results also provide evidence that--just as BRAF V600E mutations in hyperplastic polyps and benign nevi- a mutated driver gene does not imply malignant behavior per se but may set the basis for malignant transformation. The latter point may explain why rare cases of papillary hidradenoma have been reported to take a malignant course. Lastly, our genetic data may suggest treatment avenues beyond conventional surgery for some of these tumors. |
Databáze: | OpenAIRE |
Externí odkaz: |