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　　近日，在《Nature》雜志上發(fā)表了一篇文章顯示，昆士蘭大學(xué)研究所分子生物科學(xué)（IMB）教授Sean Grimmond和Kinghorn癌癥中心教授Andrew Biankin領(lǐng)導(dǎo)100多名研究人員，測(cè)序了100胰腺腫瘤的基因組，并與正常組織相比，以確定導(dǎo)致這種癌癥的基因變化。

　　分析報(bào)告由澳大利亞國(guó)際癌癥基因組協(xié)會(huì)（ICGC）完成，該團(tuán)隊(duì)它匯集了世界腫瘤領(lǐng)域頂尖科學(xué)家，該團(tuán)隊(duì)共識(shí)別了50個(gè)不同類(lèi)型的癌癥遺傳驅(qū)動(dòng)因素。

　　結(jié)果發(fā)現(xiàn)，合共超過(guò)2,000個(gè)突變存在基因，其中KRAS基因突變?cè)诩s90％的腫瘤樣品中都存在，1％或2％的腫瘤患者存在數(shù)百個(gè)基因突變。所以，當(dāng)腫瘤細(xì)胞雖然在顯微鏡下看起來(lái)非常相似的，但其基因分析卻能揭示細(xì)胞發(fā)生了很多變化。這表明，那些患有同種類(lèi)型癌癥的患者，可能需要完全不同的治療手段。

　　Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes

　　Andrew V. Biankin,Nicola Waddell,Karin S. Kassahn,Marie-Claude Gingras,Lakshmi B. Muthuswamy,et al.

　　Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.