| Full text | |
| Author(s): |
Alves Rosa, Reginaldo Cruz
;
Yurchenko, Andrey A.
;
Chahud, Fernando
;
Ribeiro-Silva, Alfredo
;
Brunaldi, Mariangela Ottoboni
;
Silva Jr, Wilson Araujo
;
Kannouche, Patricia L.
;
Nikolaev, Sergey
;
de Faria Ferraz, Victor Evangelista
Total Authors: 9
|
| Document type: | Journal article |
| Source: | GENETICS AND MOLECULAR BIOLOGY; v. 43, n. 4, p. 8-pg., 2020-01-01. |
| Abstract | |
Endometrial cancer (EC) harboring heterozygous POLE proofreading inactivating mutations (POLE-exo*) is associated with an increased number of somatic mutations that result in a distinctive anti-tumor immune response. However, the consequences of such POLE mutations in the context of the missing wild-type allele have not yet been described in endometrial tumors. A 72-year-old woman harboring a germline monoallelic frameshift mutation (p.Pro269fsTer26) in POLE was diagnosed with an EC having a somatic heterozygous mutation in the exonuclease domain of POLE (S459F). Targeted gene sequencing revealed an ultramutated phenotype (381 mutations/Mb) in the tumor and a 2-fold excess of mutations on the DNA leading strand. Additionally, we observed a mutational signature similar to the COSMIC signature 10, a higher mutation rate in this tumor than in endometrial tumors with heterozygous POLE-exo*, and an increased number of T lymphocytes. This is the first report of an ultramutated EC harboring a somatic POLE-exo* mutation in association with a germline loss-of-function mutation in this gene. The absence of a wild type POLE allele led to a particularly high mutational burden. (AU) | |
| FAPESP's process: | 17/04283-8 - Detection and characterization of germline mutations in cancer susceptibility genes in patients diagnosed with endometrial cancer and mismatch repair DNA system deficiency |
| Grantee: | Victor Evangelista de Faria Ferraz |
| Support Opportunities: | Regular Research Grants |