美国研究人员15日说,骨髓瘤等血液病可能由一种遗传性的基因变异引起。
纽约斯隆—凯特林癌症研究所的研究人员当天发表声明说,他们研究发现,在由血细胞异常增生引发的血液病患者中,“普遍存在”一种遗传性的JAK2变异基因,其中骨髓瘤患者中有一半以上存在这种变异基因。
声明说:“一个重要的现象是,人们一旦遗传一个JAK2变异基因,其DNA(脱氧核糖核酸)同一条单链上的另一个JAK2基因也容易发生变异。”
声明指出,这些变异并不是随机发生的,而是由DNA序列特点决定。因此,这项发现可以部分解释为何某些致病基因易发生变异,此外它也可有助于了解为什么一些特定人群是血液病的高危人群。
这项研究成果已发表在最新一期英国《自然·遗传学》杂志网络版上。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature Genetics 15 March 2009 | doi:10.1038/ng.342
A germline JAK2 SNP is associated with predisposition to the development of JAK2V617F-positive myeloproliferative neoplasms
Outi Kilpivaara1,12, Semanti Mukherjee2,3,12, Alison M Schram1, Martha Wadleigh4, Ann Mullally4,5, Benjamin L Ebert5,6, Adam Bass4,6, Sachie Marubayashi1, Adriana Heguy1, Guillermo Garcia-Manero7, Hagop Kantarjian7, Kenneth Offit8, Richard M Stone4, D Gary Gilliland4,5,6,9,10, Robert J Klein2 & Ross L Levine1,11
Polycythemia vera, essential thrombocythemia and primary myelofibrosis are myeloproliferative neoplasms (MPN) characterized by multilineage clonal hematopoiesis1, 2, 3, 4, 5. Given that the identical somatic activating mutation in the JAK2 tyrosine kinase gene (JAK2V617F) is observed in most individuals with polycythemia vera, essential thrombocythemia and primary myelofibrosis6, 7, 8, 9, 10, there likely are additional genetic events that contribute to the pathogenesis of these phenotypically distinct disorders. Moreover, family members of individuals with MPN are at higher risk for the development of MPN, consistent with the existence of MPN predisposition loci11. We hypothesized that germline variation contributes to MPN predisposition and phenotypic pleiotropy. Genome-wide analysis identified an allele in the JAK2 locus (rs10974944) that predisposes to the development of JAK2V617F-positive MPN, as well as three previously unknown MPN modifier loci. We found that JAK2V617F is preferentially acquired in cis with the predisposition allele. These data suggest that germline variation is an important contributor to MPN phenotype and predisposition.
1 Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
2 Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
3 Gerstner Sloan-Kettering Graduate School of Biomedical Sciences, New York, New York, USA.
4 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
5 Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
6 Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
7 Department of Leukemia, M.D. Anderson Cancer Center, Houston, Texas, USA.
8 Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
9 Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA.
10 Harvard Stem Cell Institute, Boston, Massachusetts, USA.
11 Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
12 These authors contributed equally to this work.