Second primary neoplasms in patients with retinoblastoma

Draper, G J; Sanders, B M; Kingston, J. E.

doi:10.1038/bjc.1986.110

Cited by 527 publications

(252 citation statements)

References 28 publications

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“…[65] The elevated risk of second primary bladder cancer among retinoblastoma survivors has been attributed to radiation treatment or cyclophosphamide chemotherapy [66][67][68]. However, Fletcher et al, found that hereditary retinoblastoma survivors who were not exposed to highdose radiation or chemotherapy had a substantially higher mortality from bladder cancer versus the general population (standardized mortality ratio [SMR] = 26.3; 95%, CI 8.5-61.4).…”

Section: High-penetrance Genesmentioning

confidence: 99%

Familial and genetic risk of transitional cell carcinoma of the urinary tract

Mueller¹,

Caporaso²,

Greene³

2008

Urologic Oncology: Seminars and Original Investigations

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Environmental exposures, including tobacco smoke and occupational exposure to aromatic amines, have been implicated in bladder cancer etiology. However, the pathogenesis of urinary bladder transitional cell carcinoma remains incompletely defined. In epidemiologic studies, family history confers a two-fold increase in bladder cancer risk, but it is uncertain whether this represents evidence of a genetic and/or a shared environmental basis for familial aggregation. Polymorphisms in genes involved in the metabolism of environmental toxins (e.g., NAT2) clearly modify individual susceptibility to bladder cancer. A genetic predisposition has also been suggested by case reports describing multiple-case families, and the development of bladder cancer in association with several well-described Mendelian disorders (e.g., HNPCC, retinoblastoma). Here we update a previouslyreported family, report a new multiple-case kindred, critically review previously-reported bladder cancer families and the epidemiologic literature related to family history of transitional cell carcinoma of the urinary tract (TCCUT) as a risk factor, as well as provide a brief summary of genetic factors that have been implicated in TCCUT risk. We conclude that familial TCCUT is either very uncommon or significantly under-reported, perhaps on the assumption that this is an environmental rather than a genetic disorder. The interaction between multiple genetic and environmental factors has made it challenging to identify genetic components responsible for many common diseases; therefore, a proposed genome-wide association study (GWAS) for urinary bladder cancer may help to clarify the etiologic role of the candidate genetic pathways reviewed here, as well as characterize gene/environment interactions that contribute to TCCUT carcinogenesis.

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Section: High-penetrance Genesmentioning

confidence: 99%

Familial and genetic risk of transitional cell carcinoma of the urinary tract

Mueller¹,

Caporaso²,

Greene³

2008

Urologic Oncology: Seminars and Original Investigations

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“…Individuals harbouring germline mutations in the Rb gene and who have retinoblastoma as children show an increased risk of melanoma as adults (Draper et al, 1986;Traboulsi et al, 1988;Eng et al, 1993;Bataille et al, 1995). In addition, three melanoma prone families have been reported to possess germline mutations in the CDK4 gene that cosegregate with the disease.…”

Section: Abstract: Familial Melanoma; Cdk6mentioning

confidence: 99%

Lack of germline CDK6 mutations in familial melanoma

et al. 2000

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Germline mutations in genes encoding several components of the retinoblastoma pathway have been linked with inherited predisposition to melanoma. Most commonly, such mutations involve CDKN2A, a cyclindependant kinase inhibitor of two kinases, CDK4 and CDK6, which phosphorylate the retinoblastoma protein (pRB) and thereby promote passage through the G 1 /S cell-cycle restriction point. Less frequently, germline mutations in the CDK4 gene have also been linked with an increased risk of melanoma. Despite the sequence and functional homology between CDK4 and CDK6, the role of germline mutations in CDK6 in melanoma predisposition is unknown. We detected no CDK6 mutations within the p16 (CDKN2A) binding domain in index cases from 60 melanoma-prone kindreds that lacked germline mutations in the coding regions of either CDKN2A or within the entire CDK4 coding region. We conclude that germline mutations in CDK6 do not make a signi®cant contribution to melanoma predisposition. Oncogene (2000) 19, 1849 ± 1852. Keywords: familial melanoma; CDK6Between 8 and 12% of melanoma cases arise in families with a genetic predisposition to the disease (Tucker and Goldstein, 1995). In a subset of these kindreds, germline coding mutations of the CDKN2A gene (on human chromosome 9p21) co-segregate with cases of melanoma (Hussussian et al., 1994;Walker et al., 1995;Dracopoli and Fountain, 1996;FitzGerald et al., 1996; NL and DH, unpublished). The CDKN2A gene product ± designated p16 ± is a cyclin-dependent kinase (CDK) inhibitor (CDKI). p16 plays a key regulatory role in the retinoblastoma (Rb) pathway at the G 1 /S cell-cycle restriction point by inhibiting the phosphorylation of Rb via CDK4/6 (Kato et al., 1993;Weinberg, 1995;Ruas and Peters, 1998). The genetic basis for melanoma in families and individuals that lack coding mutations of CDKN2A is not well understood at this time. Possible explanations include non-coding mutations of CDKN2A; alterations in other genes located at 9p21; and mutations of other major or minor melanoma predisposition genes located elsewhere in the human genome.Genetic alterations of two other members of the Rb pathway in addition to CDKN2A have been linked with an increased risk of melanoma. Individuals harbouring germline mutations in the Rb gene and who have retinoblastoma as children show an increased risk of melanoma as adults (Draper et al., 1986;Traboulsi et al., 1988;Eng et al., 1993;Bataille et al., 1995). In addition, three melanoma prone families have been reported to possess germline mutations in the CDK4 gene that cosegregate with the disease. Two of these families possess a cysteine rather than the wild-type arginine at amino acid 24 (R24C; Zuo et al., 1996). More recently, an additional mutation at position 24 (R24H) was identi®ed in a single French kindred (Sou®r et al., 1998). Moreover, the R24C (and presumably the R24H) mutant protein has a reduced a nity for p16, resulting in relaxation of control at the G1/S restriction point. CDK6 shows considerable amino acid homology with CDK4 ( Figure...

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“…This 'two hit' mechanism was first hypothesised by Knudson (Knudson, 1976) and later substantiated following cloning of RB1 (Friend et al, 1986). In patients with germline mutations, bilateral Rb tumours usually develop and patients have an increased risk of secondary cancers, in particular osteosarcoma and soft tissue sarcoma (Draper et al, 1986;Roarty et al, 1988). In the sporadic unilateral Rb tumours, both RB1 mutations are required in the same somatic cell to initiate tumour formation.…”

mentioning

confidence: 93%

High level amplification of N-MYC is not associated with adverse histology or outcome in primary retinoblastoma tumours

et al. 2002

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Twenty-five primary retinoblastoma tumours were analysed by real-time quantitative polymerase chain reaction to determine the genomic copy number of the N-MYC gene (2p24) relative to the copy number for REL, B2M, ALB, AF10 and MLL. Twenty-one of these tumours were shown by Comparative Genomic Hybridization to contain variable copy number increases of chromosomal material mapping to 2p. High level amplification (430-fold) of N-MYC was found in three tumours, none of which showed adverse histological features and all patients are surviving at between 54 and 108 months post enucleation. Furthermore, the three tumours associated with metastasis and adverse patient outcome showed normal N-MYC copy number. Although high level amplification of N-MYC is an unfavourable prognostic indicator in neuroblastoma, these data show no evidence of a correlation between amplification of N-MYC and adverse outcome in retinoblastoma.

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Second primary neoplasms in patients with retinoblastoma

Cited by 527 publications

References 28 publications

Familial and genetic risk of transitional cell carcinoma of the urinary tract

Familial and genetic risk of transitional cell carcinoma of the urinary tract

Lack of germline CDK6 mutations in familial melanoma

High level amplification of N-MYC is not associated with adverse histology or outcome in primary retinoblastoma tumours

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