Genetic alterations in Japanese extrahepatic biliary tract cancer

Noguchi, Rei; Yamaguchi, Kiyoshi; Ikenoue, Tsuneo; Terakado, Yumi; Ohta, Yasunori; Yamashita, Naohide; Kainuma, Osamu; Yokoi, Sana; Maru, Yoshiaki; Nagase, Hiroki; Furukawa, Yoichi

doi:10.3892/ol.2017.6224

Cited by 15 publications

(16 citation statements)

References 51 publications

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“…No instances of ARID1A or PIK3CA mutations were observed in the Japanese patient cohort, which contrasts with one report identifying inactivating ARID1A mutations in Japanese patients . In contrast, other reports using sequencing assays failed to find ARID1A mutations among Asian patients . In addition, TP53 mutations were more prevalent in the Chilean cohort (76%), although this difference did not reach statistical significance.…”

Section: Discussioncontrasting

confidence: 89%

“…38 In contrast, other reports using sequencing assays failed to find ARID1A mutations among Asian patients. 37,40,41 In addition, TP53 mutations were more prevalent in the Chilean cohort (76%), although this difference did not reach statistical significance. Prior reports have noted that TP53 mutations occur in 47% to 64% of patients.…”

Section: Discussionmentioning

confidence: 86%

“…In addition, TP53 mutations were more prevalent in the Chilean cohort (76%), although this difference did not reach statistical significance. Prior reports have noted that TP53 mutations occur in 47% to 64% of patients . Moreover, Chilean patients lacked ARID2 and ERBB3 mutations.…”

Section: Discussionmentioning

confidence: 92%

“…Prior reports have noted that TP53 mutations occur in 47% to 64% of patients. 37,41 Moreover, Chilean patients lacked ARID2 and ERBB3 mutations.…”

Section: Discussionmentioning

confidence: 99%

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Regional differences in gallbladder cancer pathogenesis: Insights from a multi‐institutional comparison of tumor mutations

Narayan

Creasy

Goldman

et al. 2018

Cancer

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Background Although rare in the United States, gallbladder cancer (GBCA) is a common cause of cancer death in some parts of the world. To investigate regional differences in pathogenesis and outcomes for GBCA, tumor mutations were analyzed from a sampling of specimens. Methods Primary tumors from patients with GBCA who were treated in Chile, Japan, and the United States between 1999 and 2016 underwent targeted sequencing of known cancer‐associated genes. Fisher exact and Kruskal‐Wallis tests assessed differences in clinicopathologic and genetic factors. Kaplan‐Meier methods evaluated differences in overall survival from the time of surgery between mutations. Results A total of 81 patients were included. Japanese patients (11 patients) were older (median age, 72 years [range, 54‐81 years]) compared with patients from Chile (21 patients; median age, 59 years [range, 32‐73 years]) and the United States (49 patients; median age, 66 years [range, 46‐87 years]) (P = .002) and had more well‐differentiated tumors (46% vs 0% for Chile/United States; P < .001) and fewer gallstone‐associated cancers (36% vs 67% for Chile and 69% for the United States; P = .13). Japanese patients had a median mutation burden of 6 (range, 1‐23) compared with Chile (median mutation burden, 7 [range, 3‐20]) and the United States (median mutation burden, 4 [range, 0‐27]) (P = .006). Tumors from Japanese patients lacked AT‐rich interaction domain 1A (ARID1A) and phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha (PIK3CA) mutations, whereas Chilean tumors lacked Erb‐B2 receptor tyrosine kinase 3 (ERBB3) and AT‐rich interaction domain 2 (ARID2) mutations. SMAD family member 4 (SMAD4) was found to be mutated similarly across centers (38% in Chile, 36% in Japan, and 27% in the United States; P = .68) and was univariately associated with worse overall survival (median, 10 months vs 25 months; P = .039). At least one potentially actionable gene was found to be altered in 80% of tumors. Conclusions Differences in clinicopathologic variables suggest the possibility of distinct GBCA pathogenesis in Japanese patients, which may be supported by differences in mutation pattern. Among all centers, SMAD4 mutations were detected in approximately one‐third of patients and may represent a converging factor associated with worse survival. The majority of patients carried mutations in actionable gene targets, which may inform the design of future trials.

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Section: Discussioncontrasting

confidence: 89%

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 92%

“…Prior reports have noted that TP53 mutations occur in 47% to 64% of patients. 37,41 Moreover, Chilean patients lacked ARID2 and ERBB3 mutations.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Regional differences in gallbladder cancer pathogenesis: Insights from a multi‐institutional comparison of tumor mutations

Narayan

Creasy

Goldman

et al. 2018

Cancer

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“…While no PIK3CA mutations were found in Brazil patients, 12.5%, 16.9%, and 21.4% of GBC with PIK3CA mutations were identified in USA, Japan, and Chile, respectively. 154,[203][204][205] We previously found that PIK3CA mutations E545K occurred in~5.9% of GBC, and that these patients exhibited a worse prognosis. 58,206 Epigenetic alteration of PTEN also contributes to the development of GBC as 30% GBCs exhibited PTEN promoter hypermethylated.…”

Section: Her2mentioning

confidence: 99%

Overview of current targeted therapy in gallbladder cancer

Song

et al. 2020

Sig Transduct Target Ther

111

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Gallbladder cancer (GBC) is rare, but is the most malignant type of biliary tract tumor. Unfortunately, only a small population of cancer patients is acceptable for the surgical resection, the current effective regimen; thus, the high mortality rate has been static for decades. To substantially circumvent the stagnant scenario, a number of therapeutic approaches owing to the creation of advanced technologic measures (e.g., next-generation sequencing, transcriptomics, proteomics) have been intensively innovated, which include targeted therapy, immunotherapy, and nanoparticle-based delivery systems. In the current review, we primarily focus on the targeted therapy capable of specifically inhibiting individual key molecules that govern aberrant signaling cascades in GBC. Global clinical trials of targeted therapy in GBC are updated and may offer great value for novel pathologic and therapeutic insights of this deadly disease, ultimately improving the efficacy of treatment.

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Immune checkpoint inhibitor‐related molecular markers predict prognosis in extrahepatic cholangiocarcinoma

Jin,

Wang,

Zhang

et al. 2023

Cancer Medicine

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BackgroundTherapeutic approaches for extrahepatic cholangiocarcinoma (EHCC) are limited, due to insufficient understanding to biomarkers related to prognosis and drug response. Here, we comprehensively assess the molecular characterization of EHCC with clinical implications.MethodsWhole‐exome sequencing (WES) on 37 tissue samples of EHCC were performed to evaluate genomic alterations, tumor mutational burden (TMB) and microsatellite instability (MSI).ResultsMutation of KRAS (16%) was significantly correlated to poor OS. ERBB2 mutation was associated with improved OS. ERBB2, KRAS, and ARID1A were three potentially actionable targets. TMB ≥10 mutations per megabase was detected in 13 (35.1%) cases. Six patients (16.2%) with MSIsensor scores ≥10 were found. In multivariate Cox analysis, patients with MSIsensor sore exceed a certain threshold (MSIsensor score ≥0.36, value approximately above the 20th percentile as thresholds) showed a significant association with the improved OS (HR = 0.16; 95% CI: 0.056–0.46, p < 0.001), as well as patients with both TMB ≥3.47 mutations per megabase (value approximately above the 20th percentile) and MSIsensor score ≥0.36.ConclusionsTMB and MSI are potential biomarkers associated with better prognosis for EHCC patients. Furthermore, our study highlights important genetic alteration and potential therapeutic targets in EHCC.

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Genetic alterations in Japanese extrahepatic biliary tract cancer

Abstract: Abstract. Biliary tract cancer (BTC) is one of the most devastating types of malignant neoplasms worldwide. However, the mechanisms underlying the development and progression of BTC remain unresolved. BTC includes extrahepatic bile duct carcinoma (EBDC), gallbladder carcinoma (GBC)

Cited by 15 publications

References 51 publications

Regional differences in gallbladder cancer pathogenesis: Insights from a multi‐institutional comparison of tumor mutations

Regional differences in gallbladder cancer pathogenesis: Insights from a multi‐institutional comparison of tumor mutations

Overview of current targeted therapy in gallbladder cancer

Immune checkpoint inhibitor‐related molecular markers predict prognosis in extrahepatic cholangiocarcinoma

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