Frequent loss of heterozygosity on chromosome 10q in muscle-invasive transitional cell carcinomas of the bladder

Cappellen, David; S, Gil Diez de Medina; Chopin, Dominique; Thiery, Jean Paul; Radvanyi, François

doi:10.1038/sj.onc.1201154

Cited by 104 publications

(81 citation statements)

References 21 publications

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“…In addition, numerous studies of other human tumour types have suggested multiple tumour suppressor loci may be found on 10q. The predicted regions include 10q24-qter in glioblastoma multiforme (Albarosa et al, 1996;Rasheed et al, 1995), 10q23-q26 in endometrial cancer (Pei er et al, 1995), 10q21-q23 in renal cell carcinoma (Morita et al, 1991), 10q22-qter in malignant melanoma (Herbst et al, 1994), 10qter in hepatocellular carcinoma (Fujimori et al, 1991) and 10q24.1-q24.3 and 10q26.1-q26.2 in muscle-invasive bladder cancers (Cappellen et al, 1997). Each of these regions crosses the predicted SROs described in this study.…”

Section: Discussionmentioning

confidence: 99%

“…The lack of such mutations in these tumours could re¯ect the fact that PTEN inactivation is a very late event in tumorigenesis and thus, mutations are only observed in advanced stage tumours or cell lines. Alternatively, it is possible that PTEN does not represent the only or even the major tumour suppressor gene on 10q23, a possibility consistent with the ®nding of multiple distinct regions of allele loss on 10q in a variety of human tumours (Albarosa et al, 1996;Cappellen et al, 1997;Gray et al, 1996;Ittmann, 1996).…”

Section: Introductionmentioning

confidence: 88%

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Analysis of PTEN and the 10q23 region in primary prostate carcinomas

Nagai²,

et al. 1998

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Deletions involving chromosome 10q23 occur frequently in prostatic carcinomas. Recently, a novel tumour suppressor gene, PTEN, mapping to this interval, has been identi®ed. Mutation or deletion of PTEN has been observed in a proportion of prostate cancer cell lines; however, primary prostate carcinomas have not been studied. We have investigated the involvement of PTEN in primary prostatic adenocarcinomas using a panel of 51 matched normal and prostate tumour DNAs. We ®rst determined the proportion of tumours with allele loss at loci in 10q23 which span the region containing the PTEN gene. Our results show that LOH involving 10q23 is common in primary prostate carcinomas. Twenty-®ve of 51 (49%) tumours showed loss of heterozygosity (LOH) over the region spanning the PTEN locus. We next directly analysed the PTEN gene for mutations of the coding region using single strand conformation polymorphism (SSCP) and sequence analyses. Of those tumours with LOH, only a single tumour was found to carry a missense mutation in PTEN. No mutations in PTEN were identi®ed in tumours without LOH. Our results suggest either that mutation of PTEN is a late event in prostate tumorigenesis, or that another tumour suppressor gene important in prostate cancer may lie close to PTEN in 10q23.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 88%

Analysis of PTEN and the 10q23 region in primary prostate carcinomas

Nagai²,

et al. 1998

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“…The 10 remaining CIS were obtained from patients diagnosed at the Rotterdam University Hospital (Rotterdam, The Netherlands). DNA from pTa and pT1-4 tumors was extracted from samples frozen immediately in liquid nitrogen as previously described 20 or from formalin-fixed, paraffinembedded tissue, using the tissue DNA extraction kit from Qiagen (Courtaboeuf, France). All samples retained for this analysis contained more than 80% tumor cells, as assessed by histological examination.…”

Section: Tumor Samplesmentioning

confidence: 99%

Frequent FGFR3 Mutations in Papillary Non-Invasive Bladder (pTa) Tumors

Billerey

Chopin

Aubriot-Lorton

et al. 2001

The American Journal of Pathology

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428

339

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We recently identified activating mutations of fibroblast growth factor receptor 3 (FGFR3) in bladder carcinoma. In this study we assessed the incidence of FGFR3 mutations in a series of 132 bladder carcinomas: 20 carcinoma in situ (CIS), 50 pTa, 19 pT1, and 43 pT2-4. All 48 mutations identified were identical to the germinal activating mutations that cause thanatophoric dysplasia, a lethal form of dwarfism. The S249C mutation, found in 33 of the 48 mutated tumors, was the most common. The frequency of mutations was higher in pTa tumors (37 of 50, 74%) than in CIS (0 of 20, 0%; P < 0.0001), pT1 (4 of 19, 21%; P < 0.0001) and pT2-4 tumors (7 of 43, 16%; P < 0.0001). Bladder cancer is the fourth most common malignancy in men and the ninth most common in women in the Western world. In these countries, more than 90% of bladder tumors are urothelial carcinomas. At the time of initial diagnosis, approximately 80% of urothelial carcinomas are confined to the epithelium (pTa, CIS) or lamina propria (pT1), whereas the remaining 20% invade the muscularis propria (pT2, pT3, pT4). pTa lesions, the most common form of bladder carcinoma, are papillary tumors. Carcinoma in situ (CIS) are flat, cytologically highgrade carcinomas. Primary isolated CIS is a very rare entity, CIS being more commonly associated with other malignant bladder lesions. 1 Clinical evidence and molecular studies suggest that there are two pathways in bladder carcinogenesis responsible for generating two types of urothelium-confined tumors (pTa and CIS) with very different behavior. 1-6 pTa tumors are associated with a high rate of recurrence (50 -75%) but a low probability (Ͻ5%) of progression to lamina propria-invasive (pT1) and muscleinvasive (pT2-4) tumors. CIS may be the most common precursor of invasive bladder cancer because CIS shows a strong tendency to progress (40 -50%), and because most muscle-invasive lesions arise with no history of a pTa precursor lesion. This clinical evidence is supported by various molecular studies showing that CIS and invasive tumors have many genetic alterations in common, such as specific chromosomal deletions and a high frequency of p53 mutations. 2,7 In our search for new markers of carcinoma progression, we recently reported specific missense mutations in a gene encoding a growth factor receptor, fibroblast

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“…Little is known about the genetic alterations associated with the metastatic phenotype. Deletions of the long arm of chromosome 10 have been reported in many types of tumour, including colorectal carcinomas (Frayling et al, 1997), and are correlated with tumour progression and/or metastasis formation in several of these cancers, such as glial tumours (Balesaria et al, 1999), lung cancer (Petersen et al, 1998), head and neck squamous cell carcinomas (Bockmuhl et al, 2002), bladder (Cappellen et al, 1997), prostate (Komiya et al, 1996) and breast carcinomas (Bose et al, 1998). Several putative or known tumour-suppressor genes have been mapped to 10q, including BMPR1A on 10q23.2 and PTEN/MMAC1/TEP1 on 10q23.3.…”

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confidence: 99%

Loss of heterozygosity on 10q and mutational status of PTEN and BMPR1A in colorectal primary tumours and metastases

et al. 2004

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We investigated the possible role of chromosome 10q losses in colorectal cancer metastasis by carrying out an allelic imbalance study on a series of microsatellite instability-negative (MSIÀ) primary tumours (n ¼ 32) and metastases (n ¼ 36) from 49 patients. Our results demonstrate that 10q allelic losses are associated with a significant proportion (25%) of MSIÀ colorectal tumours, but are not involved in the metastatic process. PTEN and BMPR1A, two genes located in the common deleted region, were screened for mutations in samples with loss of heterozygosity. The absence or low frequency of mutations indicates that the inactivation of these genes by deletion of one allele and mutation of the other one plays only a minor role in MSIÀ tumours.

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Frequent loss of heterozygosity on chromosome 10q in muscle-invasive transitional cell carcinomas of the bladder

Cited by 104 publications

References 21 publications

Analysis of PTEN and the 10q23 region in primary prostate carcinomas

Analysis of PTEN and the 10q23 region in primary prostate carcinomas

Frequent FGFR3 Mutations in Papillary Non-Invasive Bladder (pTa) Tumors

Loss of heterozygosity on 10q and mutational status of PTEN and BMPR1A in colorectal primary tumours and metastases

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