Identification and prevalence of potentially therapeutic targetable variants of major cancer driver genes in ampullary cancer patients in India through deep sequencing

Mishra, Sudhish; Kumari, Niraj; Krishnani, Narendra; Singh, Rajneesh Kumar; Mohindra, Samir

doi:10.1016/j.cancergen.2021.08.001

Cited by 4 publications

(6 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other studies have shown a relatively high mutation rate for the SMAD4 gene [ 10 , 12 , 15 ], but no SMAD4 mutations were found in this study. SMAD4 mutations are important, particularly in pancreatic carcinogenesis, where they have been found in roughly 50% of pancreatic adenocarcinoma and 20% of invasive ampullary carcinoma [ 32 – 34 ]. Aparicio et al found a 14.4% SMAD4 mutation rate in SBA for the entire small intestine, but a rate of 7% for the jejunum [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic analysis of Japanese patients with small bowel adenocarcinoma using next-generation sequencing

et al. 2022

View full text Add to dashboard Cite

Background Small bowel adenocarcinomas (SBAs) are rare and there is little comprehensive data on SBA genomic alterations for Asian patients. This study aimed to profile genomic alterations of SBA in Japanese patients using targeted next-generation sequencing (NGS). Methods We examined 22 surgical resections from patients with primary SBA. SBA genomic alterations were analyzed by NGS. Mismatch repair (MMR) status was determined by immunohistochemical analysis. Mucin phenotypes were classified as gastric (G), intestinal (I), gastrointestinal (GI), and null (N) types on MUC2, MUC5AC, MUC6, and CD10 immunostaining. Results The most common genomic alterations found in SBA tumors were TP53 (n = 16), followed by KRAS (n = 6), APC (n = 5), PIK3CA (n = 4), CTNNB1 (n = 3), KIT (n = 2), BRAF (n = 2), CDKN2A (n = 2), and PTEN (n = 2). Deficient MMR tumors were observed in 6 out of 22 patients. Tumor mucin phenotypes included 2 in G-type, 12 in I-type, 3 in GI-type, and 5 in N-type. APC and CTNNB1 mutations were not found in G-type and GI-type tumors. KRAS mutations were found in all tumor types except for G-type tumors. TP53 mutations were found in all tumor types. Although no single gene mutation was associated with overall survival (OS), we found that KRAS mutations were associated with significant worse OS in patients with proficient MMR tumors. Conclusions SBA genomic alterations in Japanese patients do not differ significantly from those reports in Western countries. Tumor localization, mucin phenotype, and MMR status all appear to impact SBA gene mutations.

show abstract

Section: Discussionmentioning

confidence: 99%

Genetic analysis of Japanese patients with small bowel adenocarcinoma using next-generation sequencing

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Regarding the histological subtypes, a previous retrospective study reported that the frequency of SMAD4 mutations in AVC patients with the intestinal subtype (28.2%) was higher than that in patients with the pancreaticobiliary subtype (16.2%), but the P -value was 0.293 ( 57 ). The difference in the frequency was not significant ( 38 , 67 ).…”

Section: Molecular Classification Associated With Clinical Outcomesmentioning

confidence: 95%

“…Regarding the features of TP53 mutations in different histological subtypes of AVC, the difference in the proportion of TP53 mutations in the intestinal subtype and pancreaticobiliary subtype patients failed to reach statistical significance ( 55 ). A recent retrospective study ( 57 ) seemed to reveal that TP53 mutation was more frequent in AVC patients with the intestinal subtype (27/46, 58.6%) than in those with the pancreaticobiliary subtype (13/37, 35.1%, P = 0.042). This may be attributed to the limited sample sizes and the proportion of different histological subtypes in those AVC patients.…”

Section: Molecular Classification Associated With Clinical Outcomesmentioning

confidence: 96%

“…TP53 (encoding p53) is the other frequently mutated gene in patients with AVC. In all, 36%–72% of patients have been shown to have high levels of TP53 gene expression ( 35 , 47 , 53 – 57 ). Another study reported that in 82.4% (56/69) of AVC patients, abnormal p53 immunolabeling was detected ( 38 ), including nuclear accumulation of immunolabeled p53 (41.2%) and lack of p53 immunolabeling (41.2%).…”

Section: Molecular Classification Associated With Clinical Outcomesmentioning

confidence: 99%

“…The SMAD4 gene plays a pivotal role in the switch of TGF-β function by inducing cell cycle arrest and apoptosis at the early stages of tumor formation ( 64 ). The frequency of SMAD4 mutation is quite variable, ranging from 6% to 75% ( 38 , 43 , 57 , 65 , 66 ). Furthermore, a retrospective study reported that two patients (10%) with mutant SMAD4 were identified among 20 patients with KRAS mutation ( 43 ).…”

Section: Molecular Classification Associated With Clinical Outcomesmentioning

confidence: 99%

See 2 more Smart Citations

Ampulla of Vater carcinoma: advancement in the relationships between histological subtypes, molecular features, and clinical outcomes

Líu

Zhu

2023

Front. Oncol.

View full text Add to dashboard Cite

The incidence of ampulla of Vater carcinoma, a type of periampullary cancer, has been increasing at an annual percentage rate of 0.9%. However, patients with ampulla of Vater carcinoma have quite different prognoses due to the heterogeneities of the tissue origin of this carcinoma. In addition to TNM staging, histological subtypes and molecular features of ampulla of Vater carcinoma are the key factors for predicting the clinical outcomes of patients. Fortunately, with the development of testing technology, information on the histological subtypes and molecular features of ampulla of Vater carcinoma is increasingly being analyzed in-depth. Patients with the pancreaticobiliary subtype have shorter survival times. In immunohistochemical examination, high cutoff values of positive MUC1 staining can be used to accurately predict the outcome of patients. Mutant KRAS, TP53, negative SMAD4 expression, and microsatellite stability are related to poor prognosis, while the clinical value of BRCA1/BRCA2 mutations is limited for prognosis. Testing the histological subtypes and molecular characteristics of ampulla of Vater carcinoma not only is the key to prognosis analysis but also provides extra information for targeted treatment to improve the clinical outcomes of patients.

show abstract

Molecular pathways in periampullary cancer: An overview

Apurva

Sattar²,

Ali³

et al. 2022

Cellular Signalling

View full text Add to dashboard Cite

Identification and prevalence of potentially therapeutic targetable variants of major cancer driver genes in ampullary cancer patients in India through deep sequencing

Cited by 4 publications

References 34 publications

Genetic analysis of Japanese patients with small bowel adenocarcinoma using next-generation sequencing

Genetic analysis of Japanese patients with small bowel adenocarcinoma using next-generation sequencing

Ampulla of Vater carcinoma: advancement in the relationships between histological subtypes, molecular features, and clinical outcomes

Molecular pathways in periampullary cancer: An overview

Contact Info

Product

Resources

About