Altered Expression of the Retinoblastoma Gene Product: Prognostic Indicator in Bladder Cancer

Cordon‐Cardo, Carlos; Wartinger, David D.; Petrylak, Daniel P.; Dalbagni, Guido; Fair, William R.; Fuks, Zvi; Reuter, Victor E.

doi:10.1093/jnci/84.16.1251

Cited by 314 publications

(144 citation statements)

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“…53 RB gene expression is thoroughly studied in TCC, and it has been reported to be normal in the majority of the samples, but altered expression was seen in 30% to 40% of the cases. 54,55 Our results suggest that other factors may be involved in bladder TCC leading to a reduction of NF1 gene expression. Mutations in the gene control regions, down-regulation of the gene for some reason, and possible post-transcriptional regulation of NF1 protein remain issues of speculation.…”

Section: Discussionmentioning

confidence: 71%

Urinary Bladder Transitional Cell Carcinogenesis Is Associated with Down-Regulation of NF1 Tumor Suppressor Gene in Vivo and in Vitro

Aaltonen

Boström

Söderström

et al. 1999

The American Journal of Pathology

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The NF1 gene product (neurofibromin) is known to act as a tumor suppressor protein by inactivating ras. The best documented factors involved in urinary bladder transitional cell carcinoma (TCC) are ras proto-oncogene activation and p53 suppressor gene mutations. This is the first study reporting alterations in NF1 gene expression in TCC. We examined NF1 gene expression in a total of 29 surgical urinary bladder TCC specimens representing grades 1 to 3 and in three cell lines , RT4 , 5637 , and T24 (representing grades 1 to 3 , respectively). Decreased NF1 gene expression was observed in 23 of 29 (83%) TCC specimens as estimated by immunohistochemistry , the decrease being more pronounced in high-grade tumors. NF1 mRNA levels were markedly lower in TCC tissue compared with adjacent non-neoplastic urothelium, as studied by in situ hybridization for grade 3 TCC.

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Section: Discussionmentioning

confidence: 71%

Urinary Bladder Transitional Cell Carcinogenesis Is Associated with Down-Regulation of NF1 Tumor Suppressor Gene in Vivo and in Vitro

Aaltonen

Boström

Söderström

et al. 1999

The American Journal of Pathology

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“…Loss of RB1 expression, detected by IHC, has been linked to disease progression and adverse prognosis in urinary bladder UC. [49][50][51] Alterations in chromatin regulators that likely serve as tumor suppressors in urothelial carcinoma were frequently observed in this case series. Both mutations in ARID1A and KDM6A were observed in 49% of our cases, and occurred only in a mutually exclusive manner as seen in a previous study.…”

Section: Discussionmentioning

confidence: 90%

Advanced urothelial carcinoma: next-generation sequencing reveals diverse genomic alterations and targets of therapy

Wang²,

et al. 2014

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Although urothelial carcinoma (UC) of the urinary bladder generally portends a favorable prognosis, metastatic tumors often follow an aggressive clinical course. DNA was extracted from 40 lm of formalin-fixed, paraffinembedded (FFPE) sections from 35 stage IV UCs that had relapsed and progressed after primary surgery and conventional chemotherapy. Next-generation sequencing (NGS) was performed on hybridization-captured, adaptor ligation-based libraries for 3320 exons of 182 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer to at an average sequencing depth of 1164 Â and evaluated for all classes of genomic alterations (GAs). Actionable GAs were defined as those impacting the selection of targeted anticancer therapies on the market or in registered clinical trials. A total of 139 GAs were identified, with an average of 4.0 GAs per tumor (range 0-10), of which 78 (56%) were considered actionable, with an average of 2.2 per tumor (range 0-7). Twenty-nine (83%) cases harbored at least one actionable GA including: PIK3CA (9 cases; 26%); CDKN2A/B (8 cases; 23%); CCND1 (5 cases; 14%); FGFR1 (5 cases; 14%); CCND3 (4 cases; 11%); FGFR3 (4 cases; 11%); MCL1 (4 cases; 11%); MDM2 (4 cases; 11%); EGFR (2 cases, 6%); ERBB2 (HER2/neu) (2 cases, 6%); NF1 (2 cases, 6%) and TSC1 (2 cases, 6%). Notable additional alterations included TP53 (19 cases, 54%) and RB1 (6 cases; 17%). Genes involved in chromatin modification were altered by nonsense mutation, splice site mutation or frameshift indel in a mutually exclusive manner in nearly half of all cases including KDM6A (10 cases; 29%) and ARID1A (7 cases; 20%). Comprehensive NGS of 35 UCs of the bladder revealed a diverse spectrum of actionable GAs in 83% of cases, which has the potential to inform treatment decisions for patients with relapsed and metastatic disease.

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“…In fact, although decreased expression of pRb has been shown to be significantly associated with prognosis (Cordon-Cardo et al, 1992;Logothetis et al, 1992), a recent study on 173 cases failed to find any correlation between pRb and clinical outcome (Jahnson and Karlsson, 1998). However, a combined analysis of p53 and pRb in a large series (Cote et al, 1998) showed that cases with altered expression of pRb had significantly higher recurrence (P ¼ 0.0001) and lower survival rates (P ¼ 0.0002) compared to cases with normal pRb expression.…”

Section: Malignancies Of the Urinary Tractmentioning

confidence: 99%

RB family members as predictive and prognostic factors in human cancer

2006

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Altered Expression of the Retinoblastoma Gene Product: Prognostic Indicator in Bladder Cancer

Abstract: This study demonstrates that altered patterns of Rb protein expression may be an important prognostic variable in patients presenting with invasive bladder cancer.

Cited by 314 publications

References 0 publications

Urinary Bladder Transitional Cell Carcinogenesis Is Associated with Down-Regulation of NF1 Tumor Suppressor Gene in Vivo and in Vitro

Urinary Bladder Transitional Cell Carcinogenesis Is Associated with Down-Regulation of NF1 Tumor Suppressor Gene in Vivo and in Vitro

Advanced urothelial carcinoma: next-generation sequencing reveals diverse genomic alterations and targets of therapy

RB family members as predictive and prognostic factors in human cancer

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