Mutation profiling in gallbladder cancer in Indian population

Abstract

Aim Gallbladder cancer is an aggressive malignancy usually diagnosed at late stage. The molecular genetics of this cancer is heterogeneous and not well established. Mutation profiling of gallbladder cancer was performed through massarray technology with an aim to identify molecular markers involved in the tumor pathogenesis that can be helpful as markers for early diagnosis and targets for therapy. Materials and Methods Forty nine cases of gallbladder cancer were screened through Sequenom Massarray technology for 390 mutations across 30 genes in formalin fixed paraffin embedded archived tissues and the results of mutation profiling was correlated with tumor characteristics. Mutations were observed in 9 of 49 cases across four genes - TP53 (four cases), CTNNB1 (two cases), PIK3CA (two cases), and KRAS (one case). Six of these cases were well differentiated but of eight of them belonged to stage II to IV disease. Six cases had associated gallstones. Conclusion The mutation frequency found in gallbladder cancer is comparable to the data available in literature. Identification of PIK3CA and KRAS mutations would help in formulating more efficacious targeted approach for management. Studies with large number of cases would help in exploring more targets and better classification of these cancers at genetic level.

Genetic alterations in Japanese extrahepatic biliary tract cancer

“…Notably, the present study revealed relatively high frequency (22.2%) of PIK3CA mutations in Japanese BTCs, compared with previous reports (15,16,18,23,36,37,(39)(40)(41). In Caucasian BTC, the frequencies of PIK3CA mutation are limited (16,23,36,37).…”

“…Numerous previous studies have performed genetic analyses of BTC (15,16), and identified TP53 mutations in 8.2-35.7% of GBC cases (17,18), and KRAS mutations in 2-20% of GBC cases (18). KRAS mutations were identified in 20-67% of EBDC cases (19,20), and in 28.6-37.0% of AVC cases (21)(22)(23).…”

Incidental gallbladder cancer: Missing links in Pakistani population

“…Alterations in oncogenes, tumor suppressor genes, microsatellite instability and methylation of gene promoter areas act in synergy with recurrent or chronic mucosal inflammation to induce cancer although exact cause in not known [30]. Gallstones especially chronic one pose most significant risk although other suspected culprits [31] are advance age, female sex, positive family history, cholelithiasis, obesity (BMI > 30), parasitic infestations, chronic bacterial cholangitis especially by Salmonella and Helicobacter [32], porcelain gallbladder, large polyps >10 mm, heavy metals exposure and abnormal pancreaticobiliary duct junction [33] Clinical features are ominous but those harboring clue include persistent right upper quadrant pain, jaundice, nausea and weight loss [8].…”

Targeting specific molecular pathways holds promise for advanced gallbladder cancer therapy

“…The reflux of pancreatic juice into the extrahepatic biliary duct and GB results in bile changes, inducing chronic inflammation and increased cellular proliferation, which leads to epithelial hyperplasia, metaplasia and biliary tract carcinoma. APBDJ-related GBC has a frequency of KRAS mutation of 50-83% [28] of cases, particularly in codon 12, compared with GBC cases unrelated to APBDJ [29,30], where KRAS mutation presents lower frequencies (2-29%) [31][32][33]. Interestingly, KRAS mutations are also observed in 25-31% of gallbladder adenomas compared with dysplasias and carcinomas, where KRAS mutations are rare [34,35].…”