Krishnamurthy Kritika, Urioste Sophia N, Cusnir Mike, Schwartz Michael, Alghamdi Sarah, Sriganeshan Vathany, Poppiti Robert
A.M. Rywlin, MD Department of Pathology, Mount Sinai Medical Center, Miami Beach, FL.
Department of Pathology, Florida International University, Herbert Wertheim College of Medicine, Miami, FL; and.
Am J Dermatopathol. 2021 Dec 1;43(12):e185-e189. doi: 10.1097/DAD.0000000000001953.
Cutaneous malignant melanoma is an aggressive cancer that contributes significantly to cancer-related mortality. Over the years, a deeper scrutiny of melanoma biology has led to identification of diverse evolutionary patterns involving various genetic pathways. This study attempts to further understand the genetic landscape of cutaneous malignant melanoma in terms of loco-regional variations and malignant potential. Thirty-five cases of cutaneous malignant melanoma were retrieved from the archives and were classified based on location of the primary tumor and presence or absence of metastatic disease. Next-generation sequencing data consisting of base substitutions, copy number variations, indels, and rearrangements in a total of 324 genes were analyzed for recurrent genetic alterations. Statistical analysis was performed using IBM SPSS26 software. Mutations in KDM gene family were found in 62.5% of the melanomas in the head and neck as compared with 10% in melanomas of the extremity and trunk (P = 0.03). Mutations in the RAS gene family were found in 70% of melanomas in the extremities as compared to 12.5% in melanomas of the head and neck (P = 0.003). BTK gene mutations were found exclusively in melanomas of the head and neck (P = 0.032). CREBBP mutations were seen in 50% of the nonmetastatic melanomas as compared with 3.57% of metastatic melanomas (P = 0.005). This study highlights the loco-regional variations in cutaneous malignant melanoma for genetic alterations involving the KDM, RAS, and BTK gene family. In addition, the CREBBP mutational status is identified as a potential prognostic marker for predicting metastatic potential in cutaneous malignant melanomas.
皮肤恶性黑色素瘤是一种侵袭性癌症，在癌症相关死亡率中占很大比例。多年来，对黑色素瘤生物学的深入研究已导致发现涉及各种遗传途径的不同进化模式。本研究试图从局部区域差异和恶性潜能方面进一步了解皮肤恶性黑色素瘤的基因图谱。从档案中检索出35例皮肤恶性黑色素瘤病例，并根据原发性肿瘤的位置以及是否存在转移性疾病进行分类。对总共324个基因中的碱基替换、拷贝数变异、插入缺失和重排的二代测序数据进行分析，以寻找复发性基因改变。使用IBM SPSS26软件进行统计分析。发现头颈部黑色素瘤中有62.5%存在KDM基因家族突变，而四肢和躯干黑色素瘤中这一比例为10%（P = 0.03）。四肢黑色素瘤中有70%存在RAS基因家族突变，而头颈部黑色素瘤中这一比例为12.5%（P = 0.003）。BTK基因突变仅在头颈部黑色素瘤中发现（P = 0.032）。50%的非转移性黑色素瘤中可见CREBBP突变，而转移性黑色素瘤中这一比例为3.57%（P = 0.005）。本研究突出了皮肤恶性黑色素瘤在涉及KDM、RAS和BTK基因家族的基因改变方面的局部区域差异。此外，CREBBP突变状态被确定为预测皮肤恶性黑色素瘤转移潜能的潜在预后标志物。
