Impact of Tumor Grade Distribution on Genetic Alterations in Clear Cell Renal Cell Carcinoma and Prostate Cancer

Abstract

Background/Aim: A genomic analysis based on next-generation sequencing is important for deciding cancer treatment strategies. Cancer tissue sometimes displays intratumor heterogeneity and a pathologic specimen may contain more than two tumor grades. Although tumor grades are very important for the cancer prognosis, the impact of higher tumor grade distribution in a specimen used for a genomic analysis is unknown. Patients and Methods: We retrospectively analyzed the data of 61 clear cell carcinoma and 46 prostate cancer patients that were diagnosed between December 2018 and August 2022 using the GeneRead Human Comprehensive Cancer Panel or SureSelect PrePool custom Tier2. Genome annotation and curation were performed using the GenomeJack software. Results: Tumor mutation burden (TMB) was increased in proportion to the higher tumor grade distribution in grade 2 clear cell renal cell carcinoma (ccRCC). In PC, Grade Group 3/4 specimens that included an increased distribution of Gleason pattern 4 had more frequent gene mutations. Conclusion: Our results suggest the importance of selecting the maximum distribution of higher tumor grade areas to obtain results on the precise gene alterations for genomics-focused treatments.Despite recent advances in cancer treatment, advanced cancers are still incurable. Gene mutations in cancer are promising treatment targets (1, 2); thus, the precise detection of genetic alterations gives cancer patients a greater chance to receive genomics-focused treatment. Next-generation sequencing (NGS) technologies have played an important role in the detection of the genetic alterations of cancer (3). Clinically used cancer panel tests based on NGS are performed starting with DNA extracted from formalin-fixed paraffin-embedded sections or with circulating cell-free DNA extracted from blood (1, 4). In samples with <20% tumor cells in formalin-fixed paraffin-embedded sections, the sensitivity in the detection of copy number alterations (CNAs) or mutations may decrease (5, 6). The targeting of the area of the section to be used as the specimen for DNA extraction is usually determined by pathologists in order to maximize tumor cell content. Meanwhile, tumor grade, which is mostly defined by the structure and cytological features including nuclear or morphological atypia, is one of 203