dc.contributor.author |
Rosa Rosa, Juan M. |
dc.contributor.author |
Leskelä, Susanna |
dc.contributor.author |
Cristóbal Lana, Eva |
dc.contributor.author |
Santón, Almudena |
dc.contributor.author |
López García, Ma. Ángeles |
dc.contributor.author |
Muñoz, Gloria |
dc.contributor.author |
Pérez Mies, Belen |
dc.contributor.author |
Biscuola, Michele |
dc.contributor.author |
Prat, Jaime |
dc.contributor.author |
Oliva, Esther |
dc.contributor.author |
Soslow, Robert A. |
dc.contributor.author |
Matias-Guiu, Xavier |
dc.contributor.author |
Palacios, Jose |
dc.date |
2018-10-16T13:24:26Z |
dc.date |
2018-10-16T13:24:26Z |
dc.date |
2016-11-01 |
dc.date |
2018-07-24T12:16:02Z |
dc.identifier.uri |
http://hdl.handle.net/2445/125366 |
dc.format |
14 p. |
dc.format |
application/pdf |
dc.language.iso |
eng |
dc.publisher |
Nature Publishing |
dc.relation |
Versió postprint del document publicat a: https://doi.org/10.1038/modpathol.2016.132 |
dc.relation |
Modern Pathology, 2016, vol. 29, num. 11, p. 1390-1398 |
dc.relation |
https://doi.org/b10.1038/modpathol.2016.132 |
dc.rights |
(c) Springer Nature, 2016 |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
Càncer d'endometri |
dc.subject |
Genètica molecular |
dc.subject |
Endometrial cancer |
dc.subject |
Molecular genetics |
dc.title |
Molecular genetic heterogeneity in undifferentiated endometrial carcinomas |
dc.type |
info:eu-repo/semantics/article |
dc.type |
info:eu-repo/semantics/acceptedVersion |
dc.description.abstract |
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. |