Falick Michaeli Tal, Granit Mizrahi Avital, Azria Batia, Maymon Ofra, Rosenberg Shai, Monin Jonathan, Braitbart Cohen Esther, Maoz Myriam, Kadiuri Luna, Nechushtan Hovav, Meyrowitz Amichay, Peretz Tamar
Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Hebrew University Medical School, 91120, Jerusalem, Israel.
Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Ein Karem, 91120, Jerusalem, Israel.
Discov Oncol. 2024 Nov 23;15(1):698. doi: 10.1007/s12672-024-01577-x.
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.
乳腺癌中主要的致病基因(PG)包括BRCA1/2。了解患者是否携带这些改变之一具有重要意义,因为这会影响治疗管理。一个重要的问题是,BRCA1/2的种系特征在多大程度上影响肿瘤的基因组特征及其特性,以及其他环境因素可能起到什么作用。在此,我们比较了三名携带BRCA致病基因的女性(6例原发性乳腺癌)中先后发生的两种原发性乳腺癌的分子特征,其中两名患者还患有原发性肺癌。比较同一患者的两种不同肿瘤可抵消其他种系变化的影响,并可能显示出在第一种肿瘤和第二种肿瘤之间发生的其他外部损伤的可能影响。尽管如此,早期生活事件导致的表观遗传变化将存在于患者所患的所有肿瘤中。我们的分析表明,同一患者同一组织中产生的肿瘤具有相似的分子特征,尽管发生在不同时间,因为患者会受到各种外部刺激。