{"entity":{"id":"paper-biankin-pancreatic-exomes-axon-guidance-nature-2012","kind":"paper","name":"Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes","aka":[],"tldr":"Exome sequencing of 99 early-stage pancreatic cancers from the Australian genome initiative confirmed the four known drivers, added ATM and chromatin genes to the list, and found unexpected damage to nerve-guidance genes.","summary":"Exome sequencing and copy-number analysis were performed on a prospectively accrued clinical cohort of 142 early (stage I and II) sporadic pancreatic ductal adenocarcinomas; 99 informative tumours carried 2,016 non-silent mutations and 1,628 copy-number variations. Sixteen significantly mutated genes reaffirmed KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1 and uncovered EPC1, ARID2, ATM, ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6. Frequent and diverse somatic aberrations were found in axon guidance genes, particularly SLIT/ROBO signalling, also seen in Sleeping Beauty transposon mouse models.\n\nDeposited as paad_icgc on cBioPortal (KRAS mutated in 94 of 99).","asOf":"2026-09-24","links":[{"label":"Biankin et al., Nature 2012: exomes of 99 early pancreatic cancers (APGI/ICGC)","url":"https://doi.org/10.1038/nature11547"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23103869/"},{"label":"cBioPortal study paad_icgc (ICGC/APGI, Nature 2012; 99 exomes)","url":"https://www.cbioportal.org/study/summary?id=paad_icgc"}],"tags":[],"related":[],"cancers":["pancreatic","resectable-pdac"],"sections":[],"technologies":["wes-wgs"],"targets":["kras","tp53","cdkn2a","smad4","atm","arid1a","tgfbr2"],"drugs":[],"companies":[],"institutions":["garvan-institute"],"pathways":["pancreatic-cancer-signalling","tgf-beta","swi-snf-chromatin"],"terms":["somatic-mutations-wxs-wgs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2012,"doi":"10.1038/nature11547","pmid":"23103869","authors":"Biankin AV, Waddell N, Kassahn KS, et al.","paperType":"translational","findings":["16 significantly mutated genes in 99 informative exomes, including ATM, ARID2 and EPC1 as new entries.","Recurrent somatic aberrations in SLIT/ROBO axon guidance genes."],"whatItMeans":"The APGI cohort became the backbone of the QCMG whole-genome and subtype papers; ATM's entry here is the origin of its place on today's germline panels.","caveats":["Early-stage resected tumours only; bulk tissue at 2012 exome depth under-called TP53 and CDKN2A (33 and 2 of 99 on cBioPortal).","Axon guidance gene function in the disease is still unproven."],"changedPractice":false,"participants":142},"route":"/key-papers/paper-biankin-pancreatic-exomes-axon-guidance-nature-2012/","neighbours":{"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"resectable-pdac","kind":"cancer","name":"Resectable pancreatic ductal adenocarcinoma","route":"/cancers/resectable-pdac/"}],"technology":[{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"target":[{"id":"arid1a","kind":"target","name":"ARID1A","route":"/targets/arid1a/"},{"id":"atm","kind":"target","name":"ATM","route":"/targets/atm/"},{"id":"cdkn2a","kind":"target","name":"CDKN2A","route":"/targets/cdkn2a/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"smad4","kind":"target","name":"SMAD4","route":"/targets/smad4/"},{"id":"tgfbr2","kind":"target","name":"TGFBR2","route":"/targets/tgfbr2/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"institution":[{"id":"garvan-institute","kind":"institution","name":"Garvan Institute of Medical Research / Kinghorn Cancer Centre","route":"/institutions/garvan-institute/"}],"pathway":[{"id":"pancreatic-cancer-signalling","kind":"pathway","name":"Pancreatic cancer (KEGG map)","route":"/pathways/pancreatic-cancer-signalling/"},{"id":"swi-snf-chromatin","kind":"pathway","name":"SWI/SNF chromatin remodelling","route":"/pathways/swi-snf-chromatin/"},{"id":"tgf-beta","kind":"pathway","name":"TGF-β signalling","route":"/pathways/tgf-beta/"}],"term":[{"id":"somatic-mutations-wxs-wgs","kind":"term","name":"Somatic mutations from exome and genome sequencing (WXS, WGS)","route":"/terms/somatic-mutations-wxs-wgs/"}],"journal":[{"id":"nature","kind":"journal","name":"Nature","route":"/journals/nature/"}]}}