<i>KRAS</i> mutation is present in a small subset of primary urinary bladder adenocarcinomas

Alexander, Riley E.; López-Beltrán, Antonio; Montironi, Rodolfo; MacLennan, Gregory T.; Post, Kristin; Bilbo, Sarah A.; Jones, Timothy D.; Huang, Wenbin; Rao, Qiu; Sen, Joyashree D.; Meehan, Katie; Cornwell, Anita J.; Miravalle, Leticia; Liu, Cheng

doi:10.1111/j.1365-2559.2012.04309.x

Cited by 22 publications

(17 citation statements)

References 35 publications

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“…Distinction between these 2 malignancies remains a diagnostic challenge; TERT promoter mutation cannot distinguish these 2 lesions, and clinical correlation is vital before rendering a diagnosis. However, our result in conjunction with previous studies [21,22] clearly showed that primary bladder adenocarcinoma is different from UC and similar to colonic adenocarcinoma at the molecular and genetic level.…”

Section: Discussionsupporting

confidence: 87%

“…Primary adenocarcinoma of the urinary bladder (PAUB) is a rare neoplasm, accounting for less than 2% of all primary bladder malignancies and is largely overlapping with colonic carcinoma in morphology, IHC profile (both CK20+, CDX2+, and P63−) [15], and even molecular and genetic features (such as positive for KRAS mutations in some cases [21] and negative for UroVysion test [22]). Although there was a statistically significant difference in β-catenin nuclear staining between 2 groups, this staining has limited value [22].…”

Section: Discussionmentioning

confidence: 99%

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Telomerase reverse transcriptase promoter mutations in glandular lesions of the urinary bladder

Vail

Zheng

Zhou

et al. 2015

Annals of Diagnostic Pathology

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Telomerase reverse transcriptase promoter mutations in glandular lesions of the urinary bladder

Vail

Zheng

Zhou

et al. 2015

Annals of Diagnostic Pathology

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“…Therefore, determination of its mutations has a crucial role in characterization and therapy of CRC [23]. In contrast to CRC [19, 21, 25–28], KRAS mutations are rare in urothelial carcinomas and primary bladder ADCs (~5% and ~10% respectively) [17–18, 29–32]. In UrC, Sirintrapun et al observed 3 of 7 (43%) cases present with KRAS mutation, while Alexander et al found mutation in 1 of 5 UrC patients (20%) [18, 33].…”

Section: Discussionmentioning

confidence: 99%

Mutations of KRAS, NRAS, BRAF, EGFR, and PIK3CA genes in urachal carcinoma: Occurence and prognostic significance

et al. 2016

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PurposeTargeted therapy represents an attractive alternative for rare tumors such as urachal carcinoma (UrC). The aim of this study was to assess the mutations of the most commonly affected 5 genes in the targetable EGFR-pathway in UrC and comapre their frequencies to those of found in urothelial and colorectal cancer.Materials and MethodsMutational hot-spots of selected genes were tested in 22 UrC samples by pyrosequencing. Mutational patterns were compared to those published for colorectal and urothelial cancers. Furthermore, we sought correlations between mutations and clinicopathological and follow-up data.ResultsWe found 11 mutations in 10 of 22 (45%) patients. The most frequently mutated gene was KRAS (27%) followed by BRAF (18%) and NRAS (5%), while no mutations were detected in the EGFR and PIK3CA genes. No correlation was found between the mutation status and clinicopathological parameters (Sheldon/Mayo stage, tumor grade, metastases). Furthermore, none of the mutations correlated with progression-free or overall survival.ConclusionsThe mutation pattern of UrC is more similar to colorectal than to urothelial cancer. However, the mutation characteristics of UrC seems to be unique suggesting that clinical decision-making for UrC cannot be simply adopted from urothelial or colorectal carcinoma. The high occurence of EGFR-pathway mutations warrants the testing for KRAS and BRAF mutations when considering anti-EGFR therapy in UrC.

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“…A few studies have investigated molecular alterations using single gene assay in primary bladder adenocarcinoma to reveal low frequency of KRAS and TERT promoter mutations in 11.5% (3/26) and 28.5% (4/14) of primary bladder adenocarcinoma, respectively. 6,7 Although EGFR mutation or amplification and ALK rearrangement was not identified in any primary bladder adenocarcinoma, 36% of the tumors demonstrated EGFR polysomy. 8 In this study we aimed to genomically profile a cohort of primary bladder adenocarcinoma using targeted nextgeneration sequencing of 51 cancer-related genes to identify potential therapeutically useful molecular markers.…”

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confidence: 97%

Next-generation sequencing-based molecular characterization of primary urinary bladder adenocarcinoma

et al. 2017

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Primary bladder adenocarcinoma is a rare and aggressive tumor with poor clinical outcomes and no standard of care therapy. Molecular biology of this tumor is unknown due to the lack of comprehensive molecular profiling studies. The study aimed to identify genomic alterations of clinical and therapeutic significance using next-generation sequencing and compare genomic profile of primary bladder adenocarcinoma with that of high-grade urothelial carcinoma and colorectal adenocarcinoma. A cohort of 15 well-characterized primary bladder adenocarcinoma was subjected to targeted next-generation sequencing for the identification of mutations and copy-number changes in 51 cancer-related genes. Genomic profiles of 25 HGUCs and 25 colorectal adenocarcinomas using next-generation sequencing of 50 genes were compared with primary bladder adenocarcinoma. Genomic profiles were visualized using JavaScript library D3.js. A striking finding was the distinct lack of genomic alterations across the 51 genes assessed in mucinous subtype of primary bladder adenocarcinoma. Eleven of 15 primary bladder adenocarcinoma harbored at least one genomic alteration in TP53, KRAS, PIK3CA, CTNNB1, APC, TERT, FBXW7, IDH2 and RB1, many of which are novel findings and of potential therapeutic significance. CTNNB1 and APC mutations were restricted to enteric subtype only. While genomic alterations of primary bladder adenocarcinoma showed substantial overlap with colorectal adenocarcinoma, FGFR3 and HRAS mutations and APC, CTNNB1 and IDH2 alterations were mutually exclusive between primary bladder adenocarcinoma and high-grade urothelial carcinoma. These alterations affecting the MAP kinase, PI3K/Akt, Wnt, IDH (metabolic) and Tp53/Rb1 signaling pathways may provide the opportunity for defining targeted therapeutic approaches.

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KRAS mutation is present in a small subset of primary urinary bladder adenocarcinomas

Cited by 22 publications

References 35 publications

Telomerase reverse transcriptase promoter mutations in glandular lesions of the urinary bladder

Telomerase reverse transcriptase promoter mutations in glandular lesions of the urinary bladder

Mutations of KRAS, NRAS, BRAF, EGFR, and PIK3CA genes in urachal carcinoma: Occurence and prognostic significance

Next-generation sequencing-based molecular characterization of primary urinary bladder adenocarcinoma

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