Quek Camelia, Rawson Robert V, Ferguson Peter M, Shang Ping, Silva Ines, Saw Robyn P M, Shannon Kerwin, Thompson John F, Hayward Nicholas K, Long Georgina V, Mann Graham J, Scolyer Richard A, Wilmott James S
Melanoma Institute Australia, The University of Sydney, Sydney, Australia.
Sydney Medical School, The University of Sydney, Sydney, Australia.
Oncotarget. 2019 Jan 29;10(9):930-941. doi: 10.18632/oncotarget.26584.
Clinical outcomes for mucosal melanomas are often poor due to a lack of effective systemic drug therapies. Identifying driver genes in mucosal melanoma may enhance the understanding of disease pathogenesis and provide novel opportunities to develop effective therapies.
Somatic variant analysis identified (6 of 27: 22%) as the most commonly mutated gene, followed by (3 of 27: 11%). Other less frequently mutated genes (4% otherwise stated) included (7%), (7%), , , , , , , and . Recurrent SF3B1 p.R625 hotspot mutations were exclusively detected in vulvovaginal (5 of 19: 26%) and anorectal melanomas (3 of 5:60%). The only other SF3B1 mutation was a p.C1123Y mutation that occurred in a conjunctival mucosal melanoma.-mutated patients were associated with shorter overall survival (OS; 34.9 months) and progression-free survival (PFS; 16.9 months) compared to non--mutated patients (OS: 79.7 months, log-rank = 0.1172; PFS: 35.7 months, log-rank = 0.0963).
Molecular subgroups of mucosal melanoma with mutations occurred predominantly in the vulvovaginal region. mutations may have a negative prognostic impact.
Formalin-fixed biopsies were collected from 27 pathologically-confirmed mucosal melanomas. Genomic DNA was isolated from the tumor tissue and sequenced using a novel dual-strand amplicon sequencing technique to determine the frequency and types of mutations across 45 target genes.
由于缺乏有效的全身药物治疗，黏膜黑色素瘤的临床预后通常较差。确定黏膜黑色素瘤中的驱动基因可能会增进对疾病发病机制的理解，并为开发有效治疗方法提供新的机会。
体细胞变异分析确定 （27例中有6例：22%）为最常发生突变的基因，其次是 （27例中有3例：11%）。其他较少发生突变的基因（另有说明的为4%）包括 （7%）、 （7%）、 、 、 、 、 、 、 和 。复发性SF3B1 p.R625热点突变仅在阴道外阴黑色素瘤（19例中有5例：26%）和肛管直肠黑色素瘤（5例中有3例：60%）中检测到。唯一的其他SF3B1突变是发生在结膜黏膜黑色素瘤中的p.C1123Y突变。与未发生 突变的患者相比，发生 突变的患者总生存期（OS；34.9个月）和无进展生存期（PFS；16.9个月）较短（OS：79.7个月，对数秩 = 0.1172；PFS：35.7个月，对数秩 = 0.0963）。
发生 突变的黏膜黑色素瘤分子亚组主要发生在阴道外阴区域。 突变可能具有负面预后影响。
从27例经病理确诊的黏膜黑色素瘤中收集福尔马林固定的活检样本。从肿瘤组织中分离基因组DNA，并使用一种新型双链扩增子测序技术进行测序，以确定45个靶基因的突变频率和类型。
