美國(guó)研究人員15日說(shuō),，骨髓瘤等血液病可能由一種遺傳性的基因變異引起,。
紐約斯隆—凱特林癌癥研究所的研究人員當(dāng)天發(fā)表聲明說(shuō)，他們研究發(fā)現(xiàn)，在由血細(xì)胞異常增生引發(fā)的血液病患者中，“普遍存在”一種遺傳性的JAK2變異基因,，其中骨髓瘤患者中有一半以上存在這種變異基因。
聲明說(shuō)：“一個(gè)重要的現(xiàn)象是,，人們一旦遺傳一個(gè)JAK2變異基因,，其DNA（脫氧核糖核酸）同一條單鏈上的另一個(gè)JAK2基因也容易發(fā)生變異。”
聲明指出,，這些變異并不是隨機(jī)發(fā)生的,，而是由DNA序列特點(diǎn)決定。因此,，這項(xiàng)發(fā)現(xiàn)可以部分解釋為何某些致病基因易發(fā)生變異,，此外它也可有助于了解為什么一些特定人群是血液病的高危人群。
這項(xiàng)研究成果已發(fā)表在最新一期英國(guó)《自然·遺傳學(xué)》雜志網(wǎng)絡(luò)版上,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
