科學(xué)家發(fā)現(xiàn)黑色素瘤相關(guān)的新風(fēng)險基因座
澳大利亞柏格霍夫醫(yī)學(xué)研究所Matthew H. Law、美國國立衛(wèi)生研究院Maria Teresa Landi等研究人員合作，利用結(jié)合多種風(fēng)險表型的全基因組關(guān)聯(lián)薈萃分析，為皮膚黑色素瘤易感性的遺傳結(jié)構(gòu)提供了新見解。這一研究成果發(fā)表于2020年4月27日的《自然—遺傳學(xué)》。
皮膚黑素瘤的大多數(shù)遺傳易感性仍有待發(fā)現(xiàn)。研究人員利用薈萃分析全基因組關(guān)聯(lián)研究（GWAS）對36760例黑素瘤病例（67％為新分型）和375188個對照進(jìn)行了鑒定，從而確定了54個顯著（P <5×10-8）位點，并具有68個獨立的單核苷酸多態(tài)性。
不同地理區(qū)域和宿主因素的風(fēng)險估計分析表明，急性黑色素瘤亞型與色素沉著無關(guān)。結(jié)合這項薈萃分析與痣計數(shù)和頭發(fā)顏色的GWAS以及轉(zhuǎn)錄組關(guān)聯(lián)方法，研究人員發(fā)現(xiàn)了31個潛在的繼發(fā)基因座，即共計85個皮膚黑色素瘤易感基因座。
這些發(fā)現(xiàn)為皮膚黑色素瘤的遺傳結(jié)構(gòu)提供了見識，從而增強了神經(jīng)發(fā)生、色素沉著和端粒維持的重要性，并為皮膚黑色素瘤的發(fā)病機理鑒定了潛在的新途徑。
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
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