KRAS Mutation in Small Cell Lung Carcinoma and Extrapulmonary Small Cell Cancer

Abstract

Background: Lung cancer is one of the most lethal cancers. It is mainly classified into 2 groups: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Extrapulmonary small cell carcinomas (EPSCC) are very rare. The Ras oncogene controls most of the cellular functions in the cell. Overall, 21.6% of human cancers contain a Kirsten Ras (KRAS) mutation. SCLC and EPSCC have several similar features but their clinical course is different. Aims: We investigated the KRAS mutation status in SCLC and EPSCC. Study design: Mutation research. Methods: Thirty-seven SCLC and 15 EPSCC patients were included in the study. The pathological diagnoses were confirmed by a second pathologist. KRAS analysis was performed in our medical genetic department. DNA isolation was performed with primary tumor tissue using the QIAamp DNA FFPE Tissue kit (Qiagen; Hilden, Germany) in all patients. The therascreen KRAS Pyro Kit 24 V1 (Qiagen; Hilden, Germany) was used for KRAS analyses. Results: Thirty-four (91.9%) of the SCLC patients were male, while 11 (73.3%) of the EPSCC l patients were female. SCLC was more common in males, and EPSCC in females (p=0.001). A KRAS mutation was found in 6 (16.2%) if SCLC patients. The most common mutation was Q61R (CAA>CGA). Among the 15 EPSCC patients, 2 had a KRAS mutation (13.3%). When KRAS mutant and wild type patients were compared in the SCLC group, no difference was found for overall survival (p=0.6). Conclusion: In previous studies, the incidence of KRAS mutation in SCLC was 1-3%; however, it was 16.2% in our study. Therefore, there may be ethnic and geographical differences in the KRAS mutations of SCLC. As a result, KRAS mutation should not be excluded in SCLC.

Expression of the Sonic Hedgehog Embryonic Signalling Pathway Components in Matched Pre-Treatment and Relapsed Small Cell Lung Cancer Biopsies

“…While KRAS/AKT aberrant activation is a rare event in SCLC (Maitra et al, 2001;Wakuda et al, 2014;Yamamoto et al, 2008;Kodaz et al, 2016), Notch pathway signalling was found to be downregulated in 77% of 110 SCLC clinical tumour specimens, among which Notch family genomic alterations were found in 25% of cases (George et al, 2015). As Notch signals downregulate GLI1 expression via HES/HEY family members (Katoh and Katoh, 2009b), increased Shh signalling is possible in this case.…”

Progression inference for somatic mutations in cancer

“…One cluster (left side) included a series of child nodes events representing mostly mutations in BRAF [101] , [102] , EGFR [103] , [104] , NF1 [105] , and PIK3CA [106] , [107] . A second cluster was comprised of a polytree rooted by mutations in RYR2, followed by mutations in KRAS [116] , [117] , STK11 [100] , deletions in KRAS [108] , [109] , STK11 [110] , EGFR [113] , [114] , amplifications in KRAS [119] , [120] , downregulation of STK11 [100] , and upregulation of KEAP1 [111] , [112] , TP53 [115] , [100] , KRAS [118] , [100] , STK11 [100] , NF1 [121] . The third cluster of events was merely an agglomeration of child events consisting of deletions in KEAP1 [122] , amplifications of EGFR [125] , [126] and PIK3CA [127] , downregulation of NF1 [121] and KEAP1 [111] , [112] , and upregulation of EGFR [123] , [124] .…”

Role of sex hormones in lung cancer

“…identified 16.2% KRAS mutations in a cohort of 37 SCLC patients, a number much higher than that reported in previous studies for SCLC (1%–3%). 87 On the other hand, EGFR and KRAS mutational analysis in NSCLC patients showed that KRAS mutation (study frequency 28.1%) was more commonly linked with smokers (p < 0.001) and females (p = 0.01). 88…”