Mutation status of somatic EGFR and KRAS genes in Chinese patients with prostate cancer (PCa)

Abstract

Activating mutations of the epidermal growth factor receptor (EGFR) confers sensitivity to tyrosine kinase inhibitors (TKIs). In colorectal cancer and in lung adenocarcinomas, clinical trials have shown a lack of response to anti-EGFR therapy when KRAS gene mutations are present. In this study, the mutation status of specified exons of the EGFR and KRAS genes was profiled in patients with prostate cancer (PCa). Direct Sanger sequencing was used to screen for mutations in exons 19-21 of EGFR and in exon 2 of KRAS in 88 Chinese patients diagnosed with prostate adenocarcinomas. Mutations were detected in 11 patients. In nine cases (10 %), activating mutations in the region of EGFR encoding the tyrosine kinase (TK) domain were present. Deletions in exon 19 and the L858R substitution in exon 21 were "hotspot" mutations, together accounting for five (55 %) of nine cases. Many synonymous substitutions were also detected. KRAS mutations were found in two cases (2.3 % of 88). There were no cases with mutations in both EGFR and KRAS, suggesting that mutations in the two genes might be mutually exclusive. Although prognostic relevance of EGFR expression by immunohistochemistry (IHC) was observed in PCa patients in previous studies, we found no statistically significant association between EGFR or KRAS mutations and clinicopathological features (including age, smoking status, preoperative prostate-specific antigen, Gleason scores, and tumor stage). We contend that accurate profiling of the mutation status of EGFR and KRAS could improve prognostic stratification, and we suggest a potential anti-EGFR therapy for patients with PCa with EGFR mutations.

Mutation of MED12 is not a frequent occurrence in prostate cancer of Korean patients

“…The incidence of TMPRSS2-ERG gene fusion has been reported to be lower in Korean,2627 Japanese,6 and Chinese7 than in Caucasian population and PTEN inactivation has been less frequently detected in Chinese patients 7. The rate of SPOP mutation was similar26 or slightly lower28 in Korean population and the studies on KRAS or BRAF mutation have yielded inconsistent results regarding ethnic difference 293031…”

Synthetic lethality targeting LKB1 mutant and EGFR wild type human non-small cell lung cancer cells by glucose starvation and SGLT2 inhibition

“…The oncogenic EGFR and KRAS mutations are known to be mutually exclusive in NSCLC and in several other cancer types (Choughule et al, 2014;Fu et al, 2014;Kris et al, 2011;Shigematsu et al, 2005;Tam et al, 2006). Moreover, KRAS mutation is known to be negatively associated with the responsiveness of NSCLC to EGFR TKIs, serving as a negative biomarker for EGFR TKIs-based targeted therapies for NSCLC (Li et al, 2014b;Mao et al, 2010;Pao et al, 2005b).…”

Receptor tyrosine kinases: Characterisation, mechanism of action and therapeutic interests for bone cancers

“…Autocrine stimulation or overexpression of EGFR was also associated with many solid tumours. Thus, EGFR/ErbB-1 and ErbB-2 are overexpressed in lung [42] , breast [43,44] and prostate [45,46] cancer, and their expression is linked to marked aggressiveness and poor prognosis. Such observations have strengthened the therapeutic development of RTK inhibitors in the last three decades.…”

“…are characterised by their ability to dysregulate their micro-environment and especially the balance between bone apposition and bone resorption. Osteoblasts [8,45–51] and osteoclasts [8,52–54] express numerous RTKs and are then cellular targets of the corresponding ligands released in the cancer micro-environment. Based on these observations, the impact of RTK inhibitors has been assessed in bone remodelling.…”