Absence of GNAS and BRAF mutations but presence of KRAS mutation in urachal adenocarcinoma

Hang, Jen‐Fan; Pan, Chin-Chen

doi:10.1016/j.pathol.2016.11.017

Cited by 9 publications

(7 citation statements)

References 6 publications

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“…Therapeutic options include (partial) cystectomy with en bloc resection of the median umbilical ligament and umbilicus in local disease and mostly 5-fluorouracil-based chemotherapy regimes in advanced cases [5][6][7]. Recently, molecular studies have allowed more insights in the genetic background of UrC, which seems to be a distinct molecular entity [8][9][10][11][12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Urachal Cancer in Germany and the USA: An RKI/SEER Population-Based Comparison Study

et al. 2020

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Introduction: Urachal cancer (UrC) is a rare but aggressive cancer. Due to its low incidence, structured epidemiological data have only rarely been reported. To date, no valid data on UrC are available for the German population. Methods: Data on incidence and relative 5-year survival of urachal lesions (ICD-10: C67.7) were collected from all populationbased cancer registries in Germany, provided by the Robert Koch-Institut (RKI). Data were anonymized and included age, sex, and general histology (ICD-O-3). For comparison, a similar inquiry of the "Surveillance, Epidemiology, and End Results program" (SEER-18) database for the USA was conducted. Results: From 2011 to 2015, a total of 154 and 152 cases of UrC were reported for Germany (RKI) and the USA (SEER-18 area), respectively. Age-standardized incidence was 0.32/1,000,000 age-standardized cases/year in both cohorts, and elderly persons were more often affected. The major histological type was adenocarcinoma (64.9 and 81.6%). Relative 5-year survival was 54.8% (CI: 45.0-64.6) in Germany (RKI) and 64.4% (54.1-72.1) in the USA (SEER-18 cohort). Discusssion/Conclusion: The collected data demonstrate low incidence rates and similar epidemiological and clinicopathological characteristics of UrC for both registries. This is the first report of structured epidemiological data for UrC for the German population.

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Section: Introductionmentioning

confidence: 99%

Urachal Cancer in Germany and the USA: An RKI/SEER Population-Based Comparison Study

et al. 2020

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“…To date, genetic data on UrC still is scant or reported only in few cases . In addition, data on non‐adenocarcinoma UrC is completely lacking.…”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6] To date, genetic data on UrC still is scant or reported only in few cases. 4,5,[7][8][9][10][11][12] In addition, data on non-adenocarcinoma UrC is completely lacking. We therefore analyzed a large cohort of urachal adenocarcinomas in a targeted sequencing approach supplemented with in situ and protein expression analyses including evaluation of PD-L1 expression and evaluation of the MMR/MSI status.…”

Section: Introductionmentioning

confidence: 99%

Pathogenic and targetable genetic alterations in 70 urachal adenocarcinomas

Reis

Vos

Niedworok

et al. 2018

Intl Journal of Cancer

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Urachal cancer (UrC) is a rare but aggressive malignancy often diagnosed in advanced stages requiring systemic treatment. Although cytotoxic chemotherapy is of limited effectiveness, prospective clinical studies can hardly be conducted. Targeted therapeutic treatment approaches and potentially immunotherapy based on a biological rationale may provide an alternative strategy. We therefore subjected 70 urachal adenocarcinomas to targeted next-generation sequencing, conducted in situ and immunohistochemical analyses (including PD-L1 and DNA mismatch repair proteins [MMR]) and evaluated the microsatellite instability (MSI) status. The analytical findings were correlated with clinicopathological and outcome data and Kaplan-Meier and univariable/multivariable Cox regression analyses were performed. The patients had a mean age of 50 years, 66% were male and a 5-year overall survival (OS) of 58% and recurrence-free survival (RFS) of 45% was detected. Sequence variations were observed in TP53 (66%), KRAS (21%), BRAF (4%), PIK3CA (4%), FGFR1 (1%), MET (1%), NRAS (1%), and PDGFRA (1%). Gene amplifications were found in EGFR (5%), ERBB2 (2%), and MET (2%). We detected no evidence of MMR-deficiency (MMR-d)/MSI-high (MSI-h), whereas 10 of 63 cases (16%) expressed PD-L1. Therefore, anti-PD-1/PD-L1 immunotherapy approaches might be tested in UrC. Importantly, we found aberrations in intracellular signal transduction pathways (RAS/RAF/PI3K) in 31% of UrCs with potential implications for anti-EGFR therapy. Less frequent potentially actionable genetic alterations were additionally detected in ERBB2 (HER2), MET, FGFR1, and PDGFRA. The molecular profile strengthens the notion that UrC is a distinct entity on the genomic level with closer resemblance to colorectal than to bladder cancer.

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“…In another study, Cha et al ( Dienstmann et al, 2020 ) performed whole exome sequencing in adolescent and young adults with metastatic cancers; one UrC patient was identified to possess a G13D KRAS mutation. Using Sanger sequencing, Hang et al ( Hang and Pan, 2017 ) identified KRAS mutations in 5 out of 12 cases (p.G12V, 2 cases:p.G13D, 2 cases; p.G12R, 1 case).…”

Section: Evidence Synthesismentioning

confidence: 99%

Progress and prospects of targeted therapy and immunotherapy for urachal carcinoma

Zheng

Peng

et al. 2023

Front. Pharmacol.

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Introduction: Urachal carcinoma (UrC) is a rare and aggressive disease. Systematic chemotherapy shows limited efficacy in patients with advanced disease, while targeted therapy and immunotherapy may provide a reasonable alternative for specific populations. The molecular pattern of colorectal cancer (CRC) have recently been identified; this understanding has significantly influenced the clinical management of CRC in terms of molecular-targeted therapy. Although some genetic alterations have been associated with UrC, there is still no systematic overview of the molecular profile of this rare malignancy.Methods: In this review, we comprehensively discuss the molecular profile of UrC and further identify potential targets for the personalized treatment of UrC as well as immune checkpoint inhibitors that represent underlying biomarkers. A systematic literature search was carried out by searching the PubMed, EMBASE, and Web of Science databases to identify all literature related to targeted therapy and immunotherapy in urachal carcinoma from inception to February 2023.Results: A total of 28 articles were eligible, and most studies included were case report sand retrospective case series. Furthermore, 420 cases of UrC were identified to analyze the association between mutations and UrC. The most commonly mutated gene in UrC was TP53 with the prevalence of 70%, followed by KRAS mutations in 28.3%, MYC mutations in 20.3%, SMAD4 mutations in 18.2% and GNAS mutations in 18%, amongst other genes.Discussion: The molecular patterns of UrC and CRC are similar yet distinct. Notably, targeted therapy, especially EGFR-targeting therapy, might provide curative efficacy for patients with UrC by applying specific molecular markers. Additional potential biomarkers for the immunotherapy of UrC are mismatch repair (MMR) status and PD-L1 expression profile. In addition, combined regimens featuring targeted agents and immune checkpoint blockers might increase antitumor activity and exert better efficacy in UrC patients with specific mutational burden.

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Absence of GNAS and BRAF mutations but presence of KRAS mutation in urachal adenocarcinoma

Cited by 9 publications

References 6 publications

Urachal Cancer in Germany and the USA: An RKI/SEER Population-Based Comparison Study

Urachal Cancer in Germany and the USA: An RKI/SEER Population-Based Comparison Study

Pathogenic and targetable genetic alterations in 70 urachal adenocarcinomas

Progress and prospects of targeted therapy and immunotherapy for urachal carcinoma

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