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2015年12月31日 讯 /生物谷BIOON/ –最近，来自圣犹大儿童研究医院的研究人员开发了一种新型的网络应用和数据装置，其就为全球科学家们提供了强大的交互工具帮助他们理解引发儿童癌症的各种突变，相关研究刊登于Nature Genetics杂志上。这种特殊的工具名为ProteinPaint，其可以帮助有效地揭示改变编码蛋白指令且引发儿童癌症的突变，该工具可为当前的工具提供关键的信息，比如其可以揭示突变是新诊断出的还是复发出现的，或者突变是否是在所有细胞中发生或者仅是在癌症中发生的。
ProteinPaint工具的新型交互图谱可以帮助科学家们观察分析单一基因及编码的蛋白所发生的所有突变，其中就包括突变类型、癌症亚型的频率及蛋白结构域的位置，相关的信息或可帮助揭示癌症的起源、进展及复发的机制。Jinghui Zhang博士说道，新型工具对于帮助科学家们利用基因组数据进行癌症研究非常关键，而我们开发的ProteinPaint就可以帮助挖掘大量癌症基因组的数据以供科学家们进行研究。
目前存在多种类型的突变可以干扰编码蛋白的基因，以至于最终引发癌症，ProteinPaint工具可以整合来自多个数据装置中的突变信息，从而就增强了其功能，目前ProteinPaint工具中包含了在1000多名患21种类型癌症儿童中发现的几乎27500种突变的信息，而且这些数据也将会在近日进行更新。
该工具同时还可以对928名儿童中的36种癌症亚型肿瘤进行RNA序列数据的绘制，从而帮助追踪突变如何影响基因的表达，而与此同时进行全基因组测序就可以帮助揭示有机体的完整DNA组成；如今ProteinPaint工具重点对儿童癌症进行研究，其也具有帮助研究其它疾病的潜力，比如镰刀形细胞病等。最后研究者还补充道，该工具还会用于儿童癌症的种系突变研究，而相关研究也于近日刊登于国际杂志the New England Journal of Medicine上。（基因宝jiyinbao.com）
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Exploring genomic alteration in pediatric cancer using ProteinPaint
Xin Zhou, Michael N Edmonson, Mark R Wilkinson, Aman Patel, Gang Wu, Yu Liu, Yongjin Li, Zhaojie Zhang, Michael C Rusch, Matthew Parker, Jared Becksfort, James R Downing & Jinghui Zhang
Genomic information about predisposing germline mutations in normal cells as well as acquired somatic lesions in cancer cells will enable the development and delivery of individualized cancer therapies. Ongoing global initiatives have shown that the spectra of somatic and germline genetic lesions in pediatric cancer are distinct from…
Germline Mutations in Predisposition Genes in Pediatric Cancer
Jinghui Zhang, Ph.D., Michael F. Walsh, M.D., Gang Wu, Ph.D., Michael N. Edmonson, B.A., Tanja A. Gruber, M.D., Ph.D., John Easton, Ph.D., Dale Hedges, Ph.D., Xiaotu Ma, Ph.D., Xin Zhou, Ph.D., Donald A. Yergeau, Ph.D., Mark R. Wilkinson, B.S., Bhavin Vadodaria, B.A., Xiang Chen, Ph.D., Rose B. McGee, M.S., Stacy Hines-Dowell, D.N.P., Regina Nuccio, M.S., Emily Quinn, M.S., Sheila A. Shurtleff, Ph.D., Michael Rusch, B.A., Aman Patel, M.S., Jared B. Becksfort, M.S., Shuoguo Wang, Ph.D., Meaghann S. Weaver, M.D., Li Ding, Ph.D., Elaine R. Mardis, Ph.D., Richard K. Wilson, Ph.D., Amar Gajjar, M.D., David W. Ellison, M.D., Ph.D., Alberto S. Pappo, M.D., Ching-Hon Pui, M.D., Kim E. Nichols, M.D., and James R. Downing, M.D.
BACKGROUND The prevalence and spectrum of predisposing mutations among children and adolescents with cancer are largely unknown. Knowledge of such mutations may improve the understanding of tumorigenesis, direct patient care, and enable genetic counseling of patients and families. METHODS In 1120 patients younger than 20 years of age, we sequenced the whole genomes (in 595 patients), whole exomes (in 456), or both (in 69). We analyzed the DNA sequences of 565 genes, including 60 that have been associated with autosomal dominant cancer-predisposition syndromes, for the presence of germline mutations. The pathogenicity of the mutations was determined by a panel of medical experts with the use of cancer-specific and locus-specific genetic databases, the medical literature, computational predictions, and second hits identified in the tumor genome. The same approach was used to analyze data from 966 persons who did not have known cancer in the 1000 Genomes Project, and a similar approach was used to analyze data from an autism study (from 515 persons with autism and 208 persons without autism). RESULTS Mutations that were deemed to be pathogenic or probably pathogenic were identified in 95 patients with cancer (8.5%), as compared with 1.1% of the persons in the 1000 Genomes Project and 0.6% of the participants in the autism study. The most commonly mutated genes in the affected patients were TP53 (in 50 patients), APC (in 6), BRCA2 (in 6), NF1 (in 4), PMS2 (in 4), RB1 (in 3), and RUNX1 (in 3). A total of 18 additional patients had protein-truncating mutations in tumor-suppressor genes. Of the 58 patients with a predisposing mutation and available information on family history, 23 (40%) had a family history of cancer. CONCLUSIONS Germline mutations in cancer-predisposing genes were identified in 8.5% of the children and adolescents with cancer. Family history did not predict the presence of an underlying predisposition syndrome in most patients. (Funded by the American Lebanese Syrian Associated Charities and the National Cancer Institute.)