Broseghini Elisabetta, Venturi Federico, Veronesi Giulia, Scotti Biagio, Migliori Marina, Marini Desy, Ricci Claudio, Casadei Riccardo, Ferracin Manuela, Dika Emi
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
Pigment Cell Melanoma Res. 2025 Jan;38(1):e13210. doi: 10.1111/pcmr.13210. Epub 2024 Nov 28.
Cutaneous melanoma (CM) and pancreatic cancer are aggressive tumors whose incidences are rapidly increasing in the last years. This review aims to provide a complete and update description about mutational landscape in CM and pancreatic cancer, focusing on similarities of these two apparently so different tumors in terms of site, type of cell involved, and embryonic origin. The familial forms of CM and pancreatic cancers are often characterized by a common mutated gene, namely CDKN2A. In fact, a germline mutation in CDKN2A gene can be responsible for the development of the familial atypical multiple mole and melanoma syndrome (FAMMM), which is characterized by melanomas and pancreatic cancer development. Sporadic melanoma and pancreatic cancer showed different key-driven genes. The open-access resource cBioPortal has been explored to deepen and investigate the common mutational landscape of these two tumors. We investigated the common mutated genes found in both melanoma and pancreatic cancer with a frequency of at least 5% of tested patients and copy number alterations with a frequency of at least of 3%. Data showed that 18 mutated genes and 3 copy number alterations are present in both melanoma and pancreatic cancers types. Since we found two patients that developed both melanoma and pancreatic cancer, we compared mutation landscape between the two tumors and identified a pathogenic variant in BRCA2 gene. This review gives valuable insights into the genetic underpinnings of melanoma and pancreatic cancer, urging the continued exploration and research of new genetic biomarkers able to identify patients and families at high risk of developing both cancers and to address to screening and to an effective clinical management of the patient.
皮肤黑色素瘤（CM）和胰腺癌是侵袭性肿瘤，其发病率在过去几年中迅速上升。本综述旨在全面且更新地描述CM和胰腺癌的突变图谱，重点关注这两种明显不同的肿瘤在部位、涉及的细胞类型和胚胎起源方面的相似性。CM和胰腺癌的家族形式通常以一个共同的突变基因，即CDKN2A为特征。事实上，CDKN2A基因的种系突变可能导致家族性非典型多发性痣和黑色素瘤综合征（FAMMM）的发生，其特征为黑色素瘤和胰腺癌的发展。散发性黑色素瘤和胰腺癌表现出不同的关键驱动基因。我们利用开放获取资源cBioPortal来深入研究和调查这两种肿瘤的共同突变图谱。我们调查了在黑色素瘤和胰腺癌中均发现的、在至少5%的受试患者中出现的常见突变基因以及在至少3%的受试患者中出现的拷贝数改变。数据显示，黑色素瘤和胰腺癌这两种类型中均存在18个突变基因和3种拷贝数改变。由于我们发现了两名同时患黑色素瘤和胰腺癌的患者，我们比较了这两种肿瘤之间的突变图谱，并在BRCA2基因中鉴定出一个致病变体。本综述为黑色素瘤和胰腺癌的遗传基础提供了有价值的见解，促使人们继续探索和研究新的遗传生物标志物，以便能够识别有患这两种癌症高风险的患者和家族，并指导患者的筛查和有效的临床管理。
