科学家发现黑色素瘤相关的新风险基因座_黑色素瘤

澳大利亚柏格霍夫医学研究所Matthew H. Law、美国国立卫生研究院Maria Teresa Landi等研究人员合作，利用结合多种风险表型的全基因组关联荟萃分析，为皮肤黑色素瘤易感性的遗传结构提供了新见解。这一研究成果发表于2020年4月27日的《自然—遗传学》。

皮肤黑素瘤的大多数遗传易感性仍有待发现。研究人员利用荟萃分析全基因组关联研究（GWAS）对36760例黑素瘤病例（67％为新分型）和375188个对照进行了鉴定，从而确定了54个显著（P <5×10-8）位点，并具有68个独立的单核苷酸多态性。

不同地理区域和宿主因素的风险估计分析表明，急性黑色素瘤亚型与色素沉着无关。结合这项荟萃分析与痣计数和头发颜色的GWAS以及转录组关联方法，研究人员发现了31个潜在的继发基因座，即共计85个皮肤黑色素瘤易感基因座。

这些发现为皮肤黑色素瘤的遗传结构提供了见识，从而增强了神经发生、色素沉着和端粒维持的重要性，并为皮肤黑色素瘤的发病机理鉴定了潜在的新途径。

附：英文原文
Title: Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility

Author: Maria Teresa Landi, D. Timothy Bishop, Stuart MacGregor, Mitchell J. Machiela, Alexander J. Stratigos, Paola Ghiorzo, Myriam Brossard, Donato Calista, Jiyeon Choi, Maria Concetta Fargnoli, Tongwu Zhang, Monica Rodolfo, Adam J. Trower, Chiara Menin, Jacobo Martinez, Andreas Hadjisavvas, Lei Song, Irene Stefanaki, Richard Scolyer, Rose Yang, Alisa M. Goldstein, Miriam Potrony, Katerina P. Kypreou, Lorenza Pastorino, Paola Queirolo, Cristina Pellegrini, Laura Cattaneo, Matthew Zawistowski, Pol Gimenez-Xavier, Arantxa Rodriguez, Lisa Elefanti, Siranoush Manoukian, Licia Rivoltini, Blair H. Smith, Maria A. Loizidou, Laura Del Regno, Daniela Massi, Mario Mandala, Kiarash Khosrotehrani, Lars A. Akslen, Christopher I. Amos, Per A. Andresen, Marie-Franoise Avril, Esther Azizi, H. Peter Soyer, Veronique Bataille, Bruna Dalmasso, Lisa M. Bowdler, Kathryn P. Burdon, Wei V. Chen, Veryan Codd, Jamie E. Craig, Tadeusz Dbniak, Mario Falchi, Shenying Fang, Eitan Friedman, Sarah Simi, Pilar Galan, Zaida Garcia-Casado, Elizabeth M. Gillanders, Scott Gordon, Adele Green, Nelleke A. Gruis, Johan Hansson, Mark Harland, Jessica Harris, Per Helsing

Issue&Volume: 2020-04-27

Abstract: Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P<5×108) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis.

DOI: 10.1038/s41588-020-0611-8

Source: https://www.nature.com/articles/s41588-020-0611-8