據(jù)2月18日的《科學(xué)-轉(zhuǎn)化醫(yī)學(xué)》雜志報(bào)道說(shuō)，研究人員研發(fā)出了通過(guò)從腫瘤DNA中尋找個(gè)性化的生物標(biāo)記來(lái)追蹤癌癥的一種新的技術(shù),。 控制癌癥細(xì)胞需要有監(jiān)控殘余和復(fù)發(fā)腫瘤的能力,，以期評(píng)估相關(guān)的治療是否有效,。 根據(jù)發(fā)現(xiàn)在DNA中與癌癥有關(guān)的變化，Personalized Analysis of Rearranged Ends 或 PARE的手段通過(guò)搜尋手術(shù)后或在藥物治療時(shí)殘留癌癥細(xì)胞所留下的遺傳學(xué)“面包屑蹤跡”而提供人們一種具有高精確度和特異性的監(jiān)控腫瘤的方法,。 該研究顯示,，下一代的基因測(cè)序技術(shù)已經(jīng)作好了成為個(gè)體化治療癌癥病人新紀(jì)元的一個(gè)重要工具的準(zhǔn)備。
人類癌癥的一種近乎普遍存在的特征就是廣泛存在的DNA 的重組,。然而在歷史上,，要達(dá)到一種可探測(cè)這種細(xì)微變化的分辨率是很困難的。如今,，Rebecca Leary及其同僚應(yīng)用PARE在4例結(jié)腸直腸癌和2例乳腺癌中尋找到了數(shù)個(gè)重組的DNA序列,。因?yàn)檫@些重組的序列并不存在于正常的DNA中（它們僅存在于腫瘤的DNA中），這些研究人員能夠創(chuàng)建基于這些獨(dú)特序列的個(gè)體化的生物標(biāo)記或“紅旗”,。他們應(yīng)用這些生物標(biāo)記來(lái)追蹤血液或其它體液樣本中的陷入在大量正常DNA中的極小量的腫瘤DNA,，它們可在手術(shù)切除腫瘤或在其它療法之后輕易地完成。文章的作者指出,，PARE代價(jià)昂貴,，要想將其廣泛用于臨床需要大大削減其成本；不過(guò),，這種方法可能會(huì)深度地改變對(duì)癌癥治療（如放療,、化療和手術(shù)）在個(gè)體患者中的功效評(píng)估。（生物谷Bioon.com）
生物谷推薦原始出處：
Sci Transl Med 17 February 2010: DOI: 10.1126/scitranslmed.3000328
S-Nitrosylation from GSNOR Deficiency Impairs DNA Repair and Promotes Hepatocarcinogenesis
Wei Wei1, Bin Li1, Martha A. Hanes2, Sanjay Kakar3, Xin Chen4 and Limin Liu1,*
1Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA.
2Department of Laboratory Animal Resources, University of Texas Health Science Center, San Antonio, TX 78229, USA.
3Department of Pathology and Veteran Affairs, University of California, San Francisco, CA 94143, USA.
4Department of Biopharmaceutical Sciences, University of California, San Francisco, CA 94143, USA.
Human hepatocellular carcinoma (HCC) is associated with elevated expression of inducible nitric oxide synthase (iNOS), but the role of nitric oxide in the pathogenesis of HCC remains unknown. We found that the abundance and activity of S-nitrosoglutathione reductase (GSNOR), a protein critical for control of protein S-nitrosylation, were significantly decreased in ~50% of patients with HCC. GSNOR-deficient mice were very susceptible to spontaneous and carcinogen-induced HCC. During inflammatory responses, the livers of GSNOR-deficient mice exhibited substantial S-nitrosylation and proteasomal degradation of the key DNA repair protein O6-alkylguanine-DNA alkyltransferase. As a result, repair of carcinogenic O6-alkylguanines in GSNOR-deficient mice was significantly impaired. Predisposition to HCC, S-nitrosylation and depletion of alkylguanine-DNA alkyltransferase, and accumulation of O6-alkylguanines were all abolished in mice deficient in both GSNOR and iNOS. Thus, our data suggest that GSNOR deficiency, through dysregulated S-nitrosylation, may promote HCC, possibly by inactivating a DNA repair system.
