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dc.contributor.authorJorissen, RN
dc.contributor.authorChristie, M
dc.contributor.authorMouradov, D
dc.contributor.authorSakthianandeswaren, A
dc.contributor.authorLi, S
dc.contributor.authorLove, C
dc.contributor.authorXu, Z-Z
dc.contributor.authorMolloy, PL
dc.contributor.authorJones, IT
dc.contributor.authorMcLaughlin, S
dc.contributor.authorWard, RL
dc.contributor.authorHawkins, NJ
dc.contributor.authorRuszkiewicz, AR
dc.contributor.authorMoore, J
dc.contributor.authorBurgess, AW
dc.contributor.authorBusam, D
dc.contributor.authorZhao, Q
dc.contributor.authorStrausberg, RL
dc.contributor.authorLipton, L
dc.contributor.authorDesai, J
dc.contributor.authorGibbs, P
dc.contributor.authorSieber, OM
dc.date.accessioned2020-12-22T02:43:29Z
dc.date.available2020-12-22T02:43:29Z
dc.date.issued2015-09-15
dc.identifierpii: bjc2015296
dc.identifier.citationJorissen, R. N., Christie, M., Mouradov, D., Sakthianandeswaren, A., Li, S., Love, C., Xu, Z. -Z., Molloy, P. L., Jones, I. T., McLaughlin, S., Ward, R. L., Hawkins, N. J., Ruszkiewicz, A. R., Moore, J., Burgess, A. W., Busam, D., Zhao, Q., Strausberg, R. L., Lipton, L. ,... Sieber, O. M. (2015). Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer. BRITISH JOURNAL OF CANCER, 113 (6), pp.979-988. https://doi.org/10.1038/bjc.2015.296.
dc.identifier.issn0007-0920
dc.identifier.urihttp://hdl.handle.net/11343/257698
dc.description.abstractBACKGROUND: APC mutations (APC-mt) occur in ∼70% of colorectal cancers (CRCs), but their relationship to prognosis is unclear. METHODS: APC prognostic value was evaluated in 746 stage I-IV CRC patients, stratifying for tumour location and microsatellite instability (MSI). Microarrays were used to identify a gene signature that could classify APC mutation status, and classifier ability to predict prognosis was examined in an independent cohort. RESULTS: Wild-type APC microsatellite stable (APC-wt/MSS) tumours from the proximal colon showed poorer overall and recurrence-free survival (OS, RFS) than APC-mt/MSS proximal, APC-wt/MSS distal and APC-mt/MSS distal tumours (OS HR⩾1.79, P⩽0.015; RFS HR⩾1.88, P⩽0.026). APC was a stronger prognostic indicator than BRAF, KRAS, PIK3CA, TP53, CpG island methylator phenotype or chromosomal instability status (P⩽0.036). Microarray analysis similarly revealed poorer survival in MSS proximal cancers with an APC-wt-like signature (P=0.019). APC status did not affect outcomes in MSI tumours. In a validation on 206 patients with proximal colon cancer, APC-wt-like signature MSS cases showed poorer survival than APC-mt-like signature MSS or MSI cases (OS HR⩾2.50, P⩽0.010; RFS HR⩾2.14, P⩽0.025). Poor prognosis APC-wt/MSS proximal tumours exhibited features of the sessile serrated neoplasia pathway (P⩽0.016). CONCLUSIONS: APC-wt status is a marker of poor prognosis in MSS proximal colon cancer.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.titleWild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer
dc.typeJournal Article
dc.identifier.doi10.1038/bjc.2015.296
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.affiliation.departmentSurgery (RMH)
melbourne.affiliation.departmentSurgery (Western Health)
melbourne.affiliation.departmentSir Peter MacCallum Department of Oncology
melbourne.affiliation.departmentMedicine and Radiology
melbourne.source.titleBritish Journal of Cancer
melbourne.source.volume113
melbourne.source.issue6
melbourne.source.pages979-988
dc.rights.licenseCC BY-NC-SA
melbourne.elementsid998994
melbourne.contributor.authorLove, Christopher
melbourne.contributor.authorMouradov, Dmitri
melbourne.contributor.authorMcLaughlin, Stephen
melbourne.contributor.authorLipton, Lara
melbourne.contributor.authorGibbs, Peter
melbourne.contributor.authorSieber, Oliver
melbourne.contributor.authorBurgess, Antony
melbourne.contributor.authorDesai, Jayesh
melbourne.contributor.authorJorissen, Robert
melbourne.contributor.authorJones, Ian
melbourne.contributor.authorChristie, Michael
melbourne.contributor.authorSAKTHIANANDESWAREN, ANURATHA
dc.identifier.eissn1532-1827
melbourne.accessrightsOpen Access


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