Role of Homologous Recombination Repair (HRR) Genes in Uterine Leiomyosarcomas: A Retrospective Analysis

Cancers

Nicola Normanno¹  Gian Franco Zannoni²  Alessia Piermattei²  Elisa De Paolis³  Maria De Bonis³  Angelo Minucci³  Francesca Ciccarone⁴  Domenica Lorusso⁴  Giovanni Scambia⁴  Gabriella Ferrandina⁴  Matteo Bruno⁴ 

[1] Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori “Fondazione G. Pascale”-IRCCS, 80131 Naples, Italy;Gynecopathology and Breast Pathology Unit, Department of Woman and Child’s Health and Public Health & Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy;Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy;UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy;

关键词: uterine sarcomas;    molecular characterization;    homologous recombination deficiency;    clinical outcomes;   

DOI  :  10.3390/cancers14081934

来源: DOAJ

【 摘 要 】

Uterine leiomyosarcomas (uLMS) is a very rare disease, and patients experience a dismal prognosis even when treated with chemotherapy. Therefore, a more in-depth molecular characterization of this disease could provide suitable data for the identification of potential target-based drugs. This retrospective, single institutional study aimed to define the frequencies of gene alterations in uLMS, especially regarding the somatic mutations of BRCA and Homologous Recombination Repair (HRR) genes, and the impact of molecular alterations on clinical outcomes. The 16-genes Next-Generation Sequencing (NGS) panel, Homologous Recombination Solution TM (HRS, Sophia Genetics, Saint Sulpice, Switzerland), was used for the molecular evaluation of samples. The majority of patients (66/105, 63%) carried at least one sequence alteration, with a prevalence of TP53 involvement followed by RAD51B, BRCA1/2, and FANCL. Patients with TP53 gene alterations experienced a significantly worse prognosis for progression free survival (PFS) and overall survival (OS) versus wild-type patients. Given the number of patients with the BRCA1/2 mutation (N = 12), we included them in the HRR patient group; there was no difference in clinical outcomes with HRR versus non-HRR. The Cox’s multivariate analysis showed that stage and TP53 gene alterations resulted in a significantly worse OS. The integration of gene networking data, such as tumor mutation burdens and cancer driver gene identification, could show a clearer discrimination of gene distribution patterns, and lead to the implementation of therapeutic targets.

【 授权许可】

Unknown