2026-04-17T14:48:06Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1253662025-12-05T12:34:03Zcom_2072_1057col_2072_478916col_2072_478917

Molecular genetic heterogeneity in undifferentiated endometrial carcinomas Rosa Rosa, Juan Manuel Leskela, Susanna Cristóbal Lana, Eva Santón, Almudena López García, Ma. Ángeles Muñoz, Gloria Pérez Mies, Belén Biscuola, Michele Prat, Jaime Oliva, Esther Soslow, Robert A. Matias-Guiu, Xavier, 1958- Palacios, José Càncer d'endometri Genètica molecular Endometrial cancer Molecular genetics Undifferentiated and dedifferentiated endometrial carcinomas are rare and highly aggressive subtypes of uterine cancer, not well characterized at a molecular level. To investigate whether dedifferentiated carcinomas carry molecular genetic alterations similar to those of pure undifferentiated carcinomas, and to gain insight into the pathogenesis of these tumors, we selected a cohort of 18 undifferentiated endometrial carcinomas, 8 of them with a well-differentiated endometrioid carcinoma component (dedifferentiated endometrioid carcinomas), and studied them by immunohistochemistry and massive parallel and Sanger sequencing. Whole-exome sequencing of the endometrioid and undifferentiated components, as well as normal myometrium, was also carried out in one case. According to The Cancer Genome Atlas classification, we distributed 95% of the undifferentiated carcinomas in this series as follows: (a) hypermutated tumors with loss of any mismatch repair protein expression and microsatellite instability (eight cases, 45%); (b) ultramutated carcinomas carrying mutations in the exonuclease domain of POLE (two cases, 11%); (c) high copy number alterations (copy-number high) tumors group exhibiting only TP53 mutations and high number of alterations detected by FISH (two cases, 11%); and (d) low copy number alterations (copy-number low) tumors with molecular alterations typical of endometrioid endometrial carcinomas (five cases, 28%). Two of the latter cases, however, also had TP53 mutations and higher number of alterations detected by FISH and could have progressed to a copy-number high phenotype. Most dedifferentiated carcinomas belonged to the hypermutated group, whereas pure undifferentiated carcinomas shared molecular genetic alterations with copy-number low or copy-number high tumors. These results indicate that undifferentiated and dedifferentiated endometrial carcinomas are molecularly heterogeneous tumors, which may have prognostic value. 2018-10-16T13:24:26Z 2018-10-16T13:24:26Z 2016-11-01 2018-07-24T12:16:02Z info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion https://hdl.handle.net/2445/125366 27491810 27895324 eng Versió postprint del document publicat a: https://doi.org/10.1038/modpathol.2016.132 Modern Pathology, 2016, vol. 29, num. 11, p. 1390-1398 https://doi.org/b10.1038/modpathol.2016.132 (c) Springer Nature, 2016 info:eu-repo/semantics/openAccess 14 p. application/pdf Nature Publishing Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))