Copy number signatures and CCNE1 amplification reveal the involvement of replication stress in high-grade endometrial tumors oncogenesis.

PURPOSE: Managing high-grade endometrial cancer in Martinique poses significant challenges. The diversity of copy number alterations in high-grade endometrial tumors, often associated with a TP53 mutation, is a key factor complicating treatment. Due to the high incidence of high-grade tumors with poor prognosis, our study aimed to characterize the molecular signature of these tumors within a cohort of 25 high-grade endometrial cases. METHODS: We conducted a comprehensive pangenomic analysis to categorize the copy number alterations involved in these tumors. Whole-Exome Sequencing (WES) and Homologous Recombination (HR) analysis were performed. The alterations obtained from the WES were classified into various signatures using the Copy Number Signatures tool available in COSMIC. RESULTS: We identified several signatures that correlated with tumor stage and disctinct prognoses. These signatures all seem to be linked to replication stress, with CCNE1 amplification identified as the primary driver of oncogenesis in over 70% of tumors analyzed. CONCLUSION: The identification of CCNE1 amplification, which is currently being explored as a therapeutic target in clinical trials, suggests new treatment strategies for high-grade endometrial cancer. This finding holds particular significance for Martinique, where access to care is challenging.

Mutation HOXB13 c.853delT in Martinican prostate cancer patients.

BACKGROUND: In Martinique, prostate cancer (Pca) incidence rates are nowadays among the highest worldwide with a high incidence of early-onset and familial forms. Despite the demonstration of a strong familial component, identification of the genetic basis for hereditary Pca is challenging. The HOXB13 germline variant G84E (rs138213197) was described in men of European descent with Pca risk. METHODS: To investigate the potential involvement of HOXB13 mutations in Martinique, we performed sequencing of the HOXB13 coding regions of 46 index cases with early-onset Pca (before the age of 51). Additional breast cancers and controls were performed. All cancer cases analyzed in this study have been observed in the context of genetic counseling. RESULTS: We identified a rare heterozygous germline variant c.853delT (p.Ter285Lysfs) rs77179853, reported only among patients of African ancestry with a minor allele frequency of 3.2%. This variant is a stop loss reported only among patients of African ancestry with a frequency of 0.2%. CONCLUSION: In conclusion, we think that this study provides supplementary arguments that HOXB13 variants are involved in Pca.