Department of Surgery, Skaraborg Hospital, Lidköping, Sweden.
Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Cancer Med. 2021 Jul;10(13):4465-4477. doi: 10.1002/cam4.3975. Epub 2021 May 31.
Breast cancer (BC) patients are frequently at risk of developing other malignancies following treatment. Although studies have been conducted to elucidate the etiology of multiple primary malignancies (MPM) after a BC diagnosis, few studies have investigated other previously diagnosed primary malignancies (OPPM) before BC. Here, genome-wide profiling was used to identify potential driver DNA copy number alterations and somatic mutations that promote the development of MPMs. To compare the genomic profiles for two primary tumors (BC and OPPM) from the same patient, tumor pairs from 26 young women (≤50 years) diagnosed with one or more primary malignancies before breast cancer were analyzed. Malignant melanoma was the most frequent OPPM, followed by gynecologic- and hematologic malignancies. However, significantly more genetic alterations were detected in BC compared to the OPPM. BC also showed more genetic similarity as a group than the tumor pairs. Clonality testing showed that genetic alterations on chromosomes 1, 3, 16, and 19 were concordant in both tumors in 13 patients. TP53 mutations were also found to be prevalent in BC, MM, and HM. Although all samples were classified as genetically unstable, chromothripsis-like patterns were primarily observed in BC. Taken together, few recurrent genetic alterations were identified in both tumor pairs that can explain the development of MPMs in the same patient. However, larger studies are warranted to further investigate key driver mutations associated with MPMs.
乳腺癌（BC）患者在治疗后常常有发生其他恶性肿瘤的风险。虽然已经有研究致力于阐明 BC 诊断后发生多种原发性恶性肿瘤（MPM）的病因，但很少有研究调查 BC 之前发生的其他已诊断原发性恶性肿瘤（OPPM）。在这里，我们使用全基因组分析来鉴定潜在的驱动 DNA 拷贝数改变和体细胞突变，以促进 MPM 的发生。为了比较同一患者的两个原发性肿瘤（BC 和 OPPM）的基因组谱，对 26 名≤50 岁的患有一种或多种原发性恶性肿瘤的年轻女性（年轻 BC 患者）的肿瘤对进行了分析。恶性黑色素瘤是最常见的 OPPM，其次是妇科和血液系统恶性肿瘤。然而，与 OPPM 相比，BC 中检测到的遗传改变明显更多。BC 作为一个群体也比肿瘤对显示出更多的遗传相似性。克隆性检测显示，在 13 名患者的两个肿瘤中，染色体 1、3、16 和 19 上的遗传改变是一致的。还发现 TP53 突变在 BC、MM 和 HM 中普遍存在。尽管所有样本均被归类为遗传不稳定，但在 BC 中主要观察到染色体重排样模式。总之，在两个肿瘤对中发现的可解释同一患者 MPM 发生的反复发生的遗传改变很少。然而，需要更大的研究来进一步调查与 MPM 相关的关键驱动突变。
