Universität zu Köln

Schultheis, Anne M., de Bruijn, Ino, Selenica, Pier, Macedo, Gabriel S., da Silva, Edaise M., Piscuoglio, Salvatore ORCID: 0000-0003-2686-2939, Jungbluth, Achim A., Park, Kay J., Klimstra, David S., Wardelmann, Eva, Hartmann, Wolfgang, Gerharz, Claus Dieter, von Petersdorff, Mareike, Buettner, Reinhard, Reis-Filho, Jorge S. and Weigelt, Britta (2022). Genomic characterization of small cell carcinomas of the uterine cervix. Mol. Oncol., 16 (4). S. 833 - 846. HOBOKEN: WILEY. ISSN 1878-0261

Full text not available from this repository.

Abstract

Small cell carcinoma (SCC) of the uterine cervix is a rare and aggressive form of neuroendocrine carcinoma, which resembles small cell lung cancer (SCLC) in its histology and poor survival rate. Here, we sought to define the genetic underpinning of SCCs of the uterine cervix and compare their mutational profiles with those of human papillomavirus (HPV)-positive head and neck squamous cell carcinomas, HPV-positive cervical carcinomas, and SCLCs using publicly available data. Using a combination of whole-exome and targeted massively parallel sequencing, we found that the nine uterine cervix SCCs, which were HPV18-positive (n = 8) or HPV16-positive (n = 1), harbored a low mutation burden, few copy number alterations, and other than TP53 in two cases no recurrently mutated genes. The majority of mutations were likely passenger missense mutations, and only few affected previously described cancer-related genes. Using RNA-sequencing, we identified putative viral integration sites on 18q12.3 and on 8p22 in two SCCs of the uterine cervix. The overall nonsilent mutation rate of uterine cervix SCCs was significantly lower than that of SCLCs, HPV-driven cervical adeno- and squamous cell carcinomas, or HPV-positive head and neck squamous cell carcinomas. Unlike SCLCs, which are reported to harbor almost universal TP53 and RB1 mutations and a dominant tobacco smoke-related signature 4, uterine cervix SCCs rarely harbored mutations affecting these genes (2/9, 22% TP53; 0% RB1) and displayed a dominant aging (67%) or APOBEC mutational signature (17%), akin to HPV-driven cancers, including cervical adeno- and squamous cell carcinomas and head and neck squamous cell carcinomas. Taken together, in contrast to SCLCs, which are characterized by highly recurrent TP53 and RB1 alterations, uterine cervix SCCs were positive for HPV leading to inactivation of the suppressors p53 and RB, suggesting that these SCCs are convergent phenotypes.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schultheis, Anne M. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Bruijn, Ino UNSPECIFIED UNSPECIFIED UNSPECIFIED Selenica, Pier UNSPECIFIED UNSPECIFIED UNSPECIFIED Macedo, Gabriel S. UNSPECIFIED UNSPECIFIED UNSPECIFIED da Silva, Edaise M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Piscuoglio, Salvatore UNSPECIFIED orcid.org/0000-0003-2686-2939 UNSPECIFIED Jungbluth, Achim A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Park, Kay J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Klimstra, David S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wardelmann, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Gerharz, Claus Dieter UNSPECIFIED UNSPECIFIED UNSPECIFIED von Petersdorff, Mareike UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Reis-Filho, Jorge S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Weigelt, Britta UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-593067
DOI:	10.1002/1878-0261.12962
Journal or Publication Title:	Mol. Oncol.
Volume:	16
Number:	4
Page Range:	S. 833 - 846
Date:	2022
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1878-0261
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MUTATIONS; GENES Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59306