据2月18日的《科学-转化医学》杂志报道说，研究人员研发出了通过从肿瘤DNA中寻找个性化的生物标记来追踪癌症的一种新的技术。 控制癌症细胞需要有监控残余和复发肿瘤的能力，以期评估相关的治疗是否有效。 根据发现在DNA中与癌症有关的变化，Personalized Analysis of Rearranged Ends 或 PARE的手段通过搜寻手术后或在药物治疗时残留癌症细胞所留下的遗传学“面包屑踪迹”而提供人们一种具有高精确度和特异性的监控肿瘤的方法。 该研究显示，下一代的基因测序技术已经作好了成为个体化治疗癌症病人新纪元的一个重要工具的准备。
人类癌症的一种近乎普遍存在的特征就是广泛存在的DNA 的重组。然而在历史上，要达到一种可探测这种细微变化的分辨率是很困难的。如今，Rebecca Leary及其同僚应用PARE在4例结肠直肠癌和2例乳腺癌中寻找到了数个重组的DNA序列。因为这些重组的序列并不存在于正常的DNA中（它们仅存在于肿瘤的DNA中），这些研究人员能够创建基于这些独特序列的个体化的生物标记或“红旗”。他们应用这些生物标记来追踪血液或其它体液样本中的陷入在大量正常DNA中的极小量的肿瘤DNA，它们可在手术切除肿瘤或在其它疗法之后轻易地完成。文章的作者指出，PARE代价昂贵，要想将其广泛用于临床需要大大削减其成本；不过，这种方法可能会深度地改变对癌症治疗（如放疗、化疗和手术）在个体患者中的功效评估。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
