近日，在《Nature》杂志上发表了一篇文章显示，昆士兰大学研究所分子生物科学（IMB）教授Sean Grimmond和Kinghorn癌症中心教授Andrew Biankin领导100多名研究人员，测序了100胰腺肿瘤的基因组，并与正常组织相比，以确定导致这种癌症的基因变化。

　　分析报告由澳大利亚国际癌症基因组协会（ICGC）完成，该团队它汇集了世界肿瘤领域顶尖科学家，该团队共识别了50个不同类型的癌症遗传驱动因素。

　　结果发现，合共超过2,000个突变存在基因，其中KRAS基因突变在约90％的肿瘤样品中都存在，1％或2％的肿瘤患者存在数百个基因突变。所以，当肿瘤细胞虽然在显微镜下看起来非常相似的，但其基因分析却能揭示细胞发生了很多变化。这表明，那些患有同种类型癌症的患者，可能需要完全不同的治疗手段。

　　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.