NDLI: Mutational profiling of the RAS, PI3K, MET and b-catenin pathways in cancer of unknown primary: a retrospective study of the Hellenic Cooperative Oncology Group

Content Provider	Springer Nature Link
Author	Pentheroudakis, G. Kotteas, E. A. Kotoula, V. Papadopoulou, K. Charalambous, E. Cervantes, A. Ciuleanu, T. Fountzilas, G. Pavlidis, N.
Copyright Year	2014
Abstract	Cancer of unknown primary origin (CUP) had a poor prognosis, determined by clinico-histological characteristics, partly due to the lack of insights on its biology. We screened tumour DNA from 87 patients with CUP for CTNNB1 (coding exons 2,3,4,5), MET (coding exon 18), PIK3CA (coding exons 9,20), KRAS (coding exons 1,2), BRAF (coding exon 15) gene mutations by using dd-sequencing and evaluated their impact on prognosis. Mutated gene incidences in the 87 CUP cases were: KRAS 11 (12.6 %), BRAF 5 (5.7 %), PIK3CA 8 (9 %), MET 6 (6.7 %) and CTNNB1 18 (20.7 %). Several mutations in the KRAS gene were not the commonly encountered mutations in other solid tumours. Activating mutations were observed in 10.2 % in KRAS, 4.5 % in BRAF, 6.6 % in PIK3CA, 4.5 % in MET, and 19.5 % in CTNNB1. Activating mutations in PIK3CA coding exon 9 were inversely correlated with MET coding exon 18 activating mutations (p = 0.036). MET activating mutations were prognostic for poor Progression-Free Survival (median PFS 5 vs 9 months, p = 0.009) and Overall Survival (median OS 7 vs 20 months, p = 0.005). The complex profile of either CTNNB1 or MET mutations also had an adverse prognostic significance (median OS 11 vs 21 months, p = 0.015). No other gene mutation exhibited prognostic significance. In multivariate analysis, poor performance status, male gender, visceral disease and adenocarcinoma histology, but not gene mutations, were independently associated with poor patient outcome. CTNNB1 gene mutations are frequent, and along with MET mutations have an adverse prognostic effect in patients with CUP.
Starting Page	761
Ending Page	769
Page Count	9
File Format	PDF
ISSN	02620898
Journal	Clinical & Experimental Metastasis
Volume Number	31
Issue Number	7
e-ISSN	15737276
Language	English
Publisher	Springer Netherlands
Publisher Date	2014-07-05
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cancer of unknown primary CTNNB1 MET KRAS BRAF PIK3CA gene mutations Prognostic factor Survival Cancer Research Biomedicine general Oncology Hematology Surgical Oncology
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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