Retinoblastoma and Osteogenic Sarcoma

François, J.

doi:10.1159/000308656

Cited by 53 publications

(18 citation statements)

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“…Genomic gains on chromosome 1q are observed in many tumor entities, including lipomas, leiomyosarcomas and osteosarcomas, [33][34][35] which occur with increased frequency in patients with hereditary Rb (second extraocular tumors). 36,37 This suggests that Rb and second extraocular tumors may have in common some of the genetic alterations that are needed for initiation and progression.…”

Section: Discussionmentioning

confidence: 99%

Genomic gains on chromosome 1q in retinoblastoma: Consequences on gene expression and association with clinical manifestation

Gratias

Schüler

Hitpass

et al. 2005

Intl Journal of Cancer

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Many retinoblastomas (Rbs) show genomic alterations in addition to mutational loss of both normal RB1 alleles. The most frequent of these changes are gains on chromosomes 1q and 6p and losses on 16q. To identify the genes targeted by gains on chromosome 1q, we used quantitative-multiplex PCR to determine DNA copy number changes in 76 primary tumors and 6 Rb cell lines. In addition, in 21 of these tumors, gene expression was analyzed by cDNA microarray hybridization. Increased copy numbers of loci on chromosome 1q were present in 34 (45%) primary tumors and in all 6 cell lines. Two regions of gain emerged, one in 1q32 and another in 1q21. Tumors with 1q gains showed higher RNA expression of several genes in these 2 regions. The clinical manifestation of tumors with and without gains was similar with regard to many aspects, including size, necrosis and calcification. However, the distribution of age at diagnosis was remarkably distinct, with earlier diagnosis in tumors without gains. This suggests that these tumors either are initiated earlier or grow faster than tumors with gains. This association with clinical manifestation indicates that gains on 1q are significant for the biology of Rb. The genes on 1q with copy number gains and overexpression are candidates that need to be tested for their individual contribution to the progression of Rb. ' 2005 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Genomic gains on chromosome 1q in retinoblastoma: Consequences on gene expression and association with clinical manifestation

Gratias

Schüler

Hitpass

et al. 2005

Intl Journal of Cancer

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“…These may include an increased risk of osteosarcoma in apparently unaffected gene carriers (Gordon, 1974;Francois, 1977a), and a generally increased risk of cancer in relatives of patients with retinoblastoma (Gordon, 1974;Bonaiti-Pellie & Briaid-Guillemot, 1980;Fedrick & Baldwin, 1978;Strong et al, 1984).…”

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confidence: 99%

Second primary neoplasms in patients with retinoblastoma

Draper¹,

Sanders²,

Kingston³

1986

Br J Cancer

527

240

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Summary In a series of 882 retinoblastoma patients, 384 known to have the genetic form of the disease and 498 others, 30 patients developed second primary neoplasms. The spectrum of these second neoplasms is discussed in relation to the forms of treatment used for the retinoblastoma. Cumulative incidence rates of second tumours in the whole series are 2.0% at 12 years after diagnosis and 4.2% after 18 years. For patients with the genetic form of retinoblastoma the cumulative incidence rate after 18 years is 8.4% for all second neoplasms and 6.0% for osteosarcomas alone. The inherent risk among survivors from genetic retinoblastoma of developing an osteosarcoma, excluding all possible effects of treatment, is estimated to be 2.2% after 18 years. Within the field of radiation treatment the cumulative incidence rate for all second neoplasms after 18 years is 6.6% and for osteosarcomas alone 3.7%. There is some evidence that patients with genetic retinoblastoma are particularly sensitive to the carcinogenic effects of radiation. The results also suggest that the use of cyclophosphamide may increase the risk of second primary neoplasms in patients with genetic retinoblastoma. The incidence rates of second primary neoplasms in retinoblastoma survivors reported here are lower than those quoted for previously published series. Evidence from this and other papers strongly suggests an association between retinoblastoma and malignant melanoma.

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“…More than one-third of these patients developed second-site tumors outside the field of radiation or in the absence of such treatment (20). Studies of families segregating for retinoblastoma also indicate a link between the bilateral eye disease and osteosarcoma: of six siblings, three developed bilateral retinoblastoma, one unilateral retinoblastoma, and one osteosarcoma (21); two siblings with bilateral retinoblastoma each subsequently developed osteosarcoma (22); offspring of a father who had had unilateral retinoblastoma included one son with bilateral retinoblastoma, one son with unilateral retinoblastoma, and one son with osteosarcoma (23); and the father of children with bilateral and unilateral retinoblastoma by two unrelated wives subsequently developed osteosarcoma (23).…”

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confidence: 99%

Osteosarcoma and retinoblastoma: a shared chromosomal mechanism revealing recessive predisposition.

Hansen¹,

Koufos²,

Gallie³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

371

134

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Survivors of the heritable form of retinoblastoma subsequently develop second primary osteosarcomas at substantially greater frequency than either the general population or survivors of nonheritable retinoblastoma. Here we present molecular genetic evidence that the development of these two disparate tumor types involves specific somatic loss of constitutional heterozygosity for the region of human chromosome 13 that includes the RBI locus. Similar events occur during the genesis of nonheritable osteosarcoma but not in several other embryonal tumors or sarcomas. These findings suggest that a conceptual approach toward defining the number of genes whose recessive mutant forms predispose to cancer is the molecular genetic analysis of clinically associated tumor types. They also suggest that the molecular basis of mixed cancer families may be the differential expression of a single pleiotropic recessive mutation by tissue specific mitotic segregation abnormalities.Retinoblastoma is one of a group of childhood tumors to which predisposition can be inherited as an autosomal dominant trait (1). This form of the disease generally affects both eyes, whereas the spontaneous form usually affects a single eye. The occurrence of retinoblastoma as both heritable and sporadic forms has allowed detailed statistical analyses, which indicate a relationship between these two forms of the disease (2-5). A locus, RBJ, which plays a role in the development of this tumor, has been localized to the q14 band of human chromosome 13 through segregation analysis (6) and by the identification of specific deletions of this chromosomal region in some retinoblastoma patients or their tumors (7)(8)(9).A model to unify these observations has been proposed (10), based on the previous hypothesis that as few as two mutations are required for malignant transformation (2-4). In this model, bilateral retinoblastoma cases have inherited a germinal mutation of the RBJ locus, which predisposes each cell to transformation by a further event. Evidence has recently been presented that suggests that these predisposing mutations are recessive at the cellular level, are expressed upon loss of the homologous wild-type allele (10-14), and occur as germ-line events in heritable cases and somatic events in sporadic cases. Several somatic chromosomal mechanisms effect this loss, including nondisjunctional loss of the homolog carrying the wild-type allele, followed by reduplication of the mutant chromosome, and mitotic recombination between the two homologs (10); the net result is a cell that is homozygous for the mutant allele at the RBI locus (14).Advances in surgical and radiotherapeutic techniques have led to survival rates exceeding 90% for retinoblastoma patients. However, survivors of the heritable, but not the spontaneous, form are at a substantially increased risk for the development of independent, second tumors (15)(16)(17)(18)(19)(20). In a recent longitudinal survey of 693 bilateral retinoblastoma cases (20), 15% developed independent second pr...

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Retinoblastoma and Osteogenic Sarcoma

Cited by 53 publications

References 8 publications

Genomic gains on chromosome 1q in retinoblastoma: Consequences on gene expression and association with clinical manifestation

Genomic gains on chromosome 1q in retinoblastoma: Consequences on gene expression and association with clinical manifestation

Second primary neoplasms in patients with retinoblastoma

Osteosarcoma and retinoblastoma: a shared chromosomal mechanism revealing recessive predisposition.

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