Tumor analysis of BRCA carriers reveals genomic similarities although separated by time

Abstract

Among the dominant pathogenic genes (PG) in breast cancer are BRCA1/2 . Knowing whether a patient carry one of these alterations is meaningful as it affects management. A substantial question is to what extent are the genomic profile of a tumor and its characteristics affected by the germline profile of BRCA1/2 and what is the possible contribution of other environmental factors. Here, we compared the molecular characteristics of two subsequent primary breast cancers in three women (6 primary breast cancers) BRCA PG carriers, and in two of them also a primary lung cancer. Comparing two different tumors in the same patient neutralizes the contribution of other germline changes, and may demonstrate possible effects of other external insults occurring between the first and second tumor. Nonetheless, epigenetic changes resulting from early life events will be present in all tumors that the patient has developed. Our analysis suggests that tumors arising from the same tissue in the same patient share similar molecular characteristics, albeit occurring in different times, as the patient is exposed to a variety of external stimuli. Supplementary Information The online version contains supplementary material available at 10.1007/s12672-024-01577-x.