一个跨国研究小组日前表示,他们发现一个决定一种罕见皮肤癌迅速自愈的基因。这一发现意味着未来或许可以研发针对这一基因的癌症治疗药物。
TGFBR1基因的突变
新加坡科学技术研究促进局说,多发性自愈性鳞状上皮癌是一种罕见的皮肤癌,它在发病初期生长迅速,但在数周后往往会自行消退。研究人员发现,其独特的自愈现象是由于TGFBR1基因不能发挥作用。他们还发现,对其他癌症而言,使这一基因不发挥作用也可以阻断癌细胞传递相关指令。
参与这一研究的苏格兰邓迪大学遗传学专家戴维·古迪说,40多年来科学家一直对这种皮肤癌的自愈现象百思不解。了解TGFBR1基因对肿瘤的影响,就可以推断一些杀死或促进癌细胞生长的药物在临床上可能产生的效果。
不过,研究小组的领导者比尔吉特·雷恩说,这一基因也是正常信息传递机制所必需的,因此“不能不分青红皂白阻止它的作用”。
该小组成员包括苏格兰、新加坡和其他地区的研究人员。他们的发现于2月28日发表在最新一期《自然·遗传学》杂志上。(生物谷Bioon.com)
生物谷推荐原文出处:
Nature Genetics doi:10.1038/ng.780
Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1
David R Goudie,1, 16 Mariella D'Alessandro,2, 16 Barry Merriman,3 Hane Lee,3 Ildikó Szeverényi,4 Stuart Avery,4 Brian D O'Connor,3 Stanley F Nelson,3 Stephanie E Coats,1 Arlene Stewart,1 Lesley Christie,5 Gabriella Pichert,6 Jean Friedel,7 Ian Hayes,8 Nigel Burrows,9 Sean Whittaker,10 Anne-Marie Gerdes,11, 12 Sigurd Broesby-Olsen,13 Malcolm A Ferguson-Smith,14 Chandra Verma,15 Declan P Lunny,4 Bruno Reversade4 & E Birgitte Lane2, 4
Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith disease (FSD), is an autosomal-dominant skin cancer condition characterized by multiple squamous-carcinoma–like locally invasive skin tumors that grow rapidly for a few weeks before spontaneously regressing, leaving scars1, 2. High-throughput genomic sequencing of a conservative estimate (24.2 Mb) of the disease locus on chromosome 9 using exon array capture identified independent mutations in TGFBR1 in three unrelated families. Subsequent dideoxy sequencing of TGFBR1 identified 11 distinct monoallelic mutations in 18 affected families, firmly establishing TGFBR1 as the causative gene. The nature of the sequence variants, which include mutations in the extracellular ligand-binding domain and a series of truncating mutations in the kinase domain, indicates a clear genotype-phenotype correlation between loss-of-function TGFBR1 mutations and MSSE. This distinguishes MSSE from the Marfan syndrome–related disorders in which missense mutations in TGFBR1 lead to developmental defects with vascular involvement but no reported predisposition to cancer.