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
Kotteas, E. A.
SourceClinical and Experimental Metastasis
Google Scholar check
MetadataΕμφάνιση πλήρους εγγραφής
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. © 2014, Springer Science+Business Media Dordrecht.
Showing items related by title, author, creator and subject.
Papageorgis, P.; Ozturk, S.; Lambert, A. W.; Neophytou, Christiana M.; Tzatsos, Alexandros; Wong, C. K.; Thiagalingam, S.; Constantinou, Andreas I. (2015)Introduction: Basal-like breast cancer (BLBC) is an aggressive subtype often characterized by distant metastasis, poor patient prognosis, and limited treatment options. Therefore, the discovery of alternative targets to ...
Prognostic significance of WNT and hedgehog pathway activation markers in cancer of unknown primary Fotopoulos, George; Goussia, Anna; Bareta, E.; Koumpis, E.; Chrisafi, S.; Bobos, M.; Malamou-Mitsi, Vassiliki D.; Fountzilas, George; Pavlidis, Nicholas; Pentheroudakis, George (2015)Background: Cancer of unknown primary (CUP) possesses distinct biology and peculiar natural history, in which the roles of the winged and hedgehog signalling pathways are unclear. Materials and methods: We constructed ...
Serous papillary peritoneal carcinoma: Unknown primary tumour, ovarian cancer counterpart or a distinct entity? A systematic review Pentheroudakis, George; Pavlidis, Nicholas (2010)Introduction: Serous peritoneal papillary carcinoma (SPPC), though managed according to ovarian cancer therapeutic principles, has been variably considered as an ovarian cancer counterpart, a peritoneal malignancy with ...