Late Extraocular Tumours in Retinoblastoma Survivors

Francois, J; Sutter, E. De; Coppieters, R; Bie, Sylvia De

doi:10.1159/000309033

Cited by 23 publications

(8 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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 primary tumors, most commonly osteosarcoma.…”

Section: Introductionmentioning

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.

370

134

View full text Add to dashboard Cite

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...

show abstract

Section: Introductionmentioning

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.

370

134

View full text Add to dashboard Cite

show abstract

“…Mutations are spread across the gene and approximately 80% of patients with hereditary mutations have bilateral disease. Hereditary retinoblastoma patients are at risk of developing and dying of second primary cancers in childhood and adolescence (Francois et al, 1980;Draper et al, 1986;Lueder et al, 1986;DerKinderen et al, 1988;Olsen et al, 1990) and excess mortality from second malignancies in retinoblastoma survivors was found to persist during long-term follow-up into adulthood. Female patients have a higher mortality from second tumours (RR ¼ 39) than males (RR ¼ 22) (Eng et al, 1993).…”

mentioning

confidence: 99%

Single-nucleotide polymorphisms in the RB1 gene and association with breast cancer in the British population

et al. 2006

View full text Add to dashboard Cite

A substantial proportion of the familial risk of breast cancer may be attributable to genetic variants each contributing a small effect. pRb controls the cell cycle and polymorphisms within it are candidates for such low penetrance susceptibility alleles, since the gene has been implicated in several human tumours, particularly breast cancer. The purpose of this study was to determine whether common variants in the RB1 gene are associated with breast cancer risk. We assessed 15 tagging single-nucleotide polymorphisms (SNPs) using a case -control study design (np4474 cases and np4560 controls). A difference in genotype frequencies was found between cases and controls for rs2854344 in intron 17 (P-trend ¼ 0.007) and rs198580 in intron 19 (P-trend ¼ 0.018). Carrying the minor allele of these SNPs appears to confer a protective effect on breast cancer risk (odd ratio (OR) ¼ 0.86 (0.76 -0.96) for rs2854344 and OR ¼ 0.80 (0.66 -0.96) for rs198580). However, after adjusting for multiple testing these associations were borderline with an adjusted P-trend ¼ 0.068 for the most significant SNP (rs2854344). The RB1 gene is not known to contain any coding SNPs with allele frequencies X5% but several intronic variants are in perfect linkage disequilibrium with the associated SNPs. Replication studies are needed to confirm the associations with breast cancer.

show abstract

“…In 23 pa-tients who received no radiation, 5 developed second tumors. These findings suggest that the retinoblastoma gene is intimately related to the development of second tumors, that these patients have a cancer diathesis, and the incidence of a second primary tumor is the same with or without radiation therapy [2,4,9]. Abramson et al [2] report that 97% of patients who develop second tumors originally had bilateral retinoblastoma [2] and that 15% of bilateral retinoblastoma patients developed second tumors [4].…”

Section: Discussionmentioning

confidence: 99%

“…Many cases of second nonocular tumors occurring in retinoblastoma patients have been reported both within the field of previous radiation and distant from the site of the original tumor [1,2,4,8,9,16,18,20]. These tumors were initially thought to be radiation induced [8] but subsequent work by Abramson et al [1] has cast doubt on this.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Metastasis or second nonocular tumor in retinoblastoma

Furniss

Jackson

1989

Eur J Plast Surg

View full text Add to dashboard Cite

A case of bilateral retinoblastoma treated by radiation therapy with the development of a second tumor in the irradiated area after three years is presented. This required an extensive complex resection with postoperative chemotherapy. It was not possible to differentiate between recurrent retinoblastoma and sarcoma. The literature on this complex situation has been extensively reviewed and is presented.

show abstract

Late Extraocular Tumours in Retinoblastoma Survivors

Cited by 23 publications

References 9 publications

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

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

Single-nucleotide polymorphisms in the RB1 gene and association with breast cancer in the British population

Metastasis or second nonocular tumor in retinoblastoma

Contact Info

Product

Resources

About