Abstract 5446: Genetic bases of testicular seminoma and non-seminoma tumors

Abstract

Abstract Testicular Germ Cell Tumor (TGCT) is the most common cancer type in men between 15-45 years old (1 per 250 men). Around 1-2% of all cases are familial (with at least two affected individuals within the same family), between 3-5% are bilateral (they develop two tumors, one in each testicle), and the rest are sporadic patients. There are two main types of histologies, seminomas and non-seminomas, and there are also tumors that contain both seminoma and non-seminoma cells, and are called mixed tumors. No great genetic differences have been found so far between them. In order to identify susceptibility genes that could explain these histological differences, we performed Whole Exome Sequencing (WES) in peripheral blood of 61 members from 17 families with at least two affected members with TGCT. Twenty one members had seminoma, seven members had non-seminomas, and nine had mixed tumor. We did not find significant genetic differences between the two histological types at the germline level. Therefore, an evaluation at a somatic level was carried out to determine if the differences between the tumor types are in the tumor. To this end, WES of blood and tumor tissue was performed in three bilateral cases with different histologies (a seminoma in one testicle and a non-seminoma in the other). The comparison between pairs of tumors from each of the patients showed that they shared in average a 30% of the somatic mutations between both the histologies. Even more, 27 genes were shared among the two tumors in the three patients. We next performed independency tests, comparing the somatic similarities and differences between the two tumors from each patient (intrapatient) and the two histologies (interpatients), which suggest a common genetic background that could predispose to testicular cancer development. We are currently performing gene ontology analysis with the genes that were shared among the pairs of tumors from each patient. Partially supported by CIBERER and FIS 16/00440 Citation Format: Paloma Martin-Gimeno, Beatriz Paumard-Hernandez, Oriol Calvete, Javier Benitez. Genetic bases of testicular seminoma and non-seminoma tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5446.