Prediction of the risk of hereditary retinoblastoma, using DNA polymorphisms within the retinoblastoma gene

Wiggs,; Nordenskjöld,; Yandell,; Rapaport,; Grondin,; Janson,; Werelius,; Petersen, Troels R.; Craft,; Riedel, Morris

doi:10.1016/0002-9394(88)90352-2

Cited by 16 publications

(20 citation statements)

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“…Experimental evidence for this hypothesis has been obtained from observations of gene deletions of a common region in several associated tumors such as retinoblastoma and osteosarcoma (6-9, 17), rhabdomyosarcoma, Wilms tumor and hepatoblastoma (18)(19)(20)(21), and acoustic neurofibromatosis and meningioma (22)(23)(24)(25). Furthermore, sporadic cases of these tumors show similar chromosome rearrangements affecting the same region to which the inherited form ofthe disease has INS 11-3 LU HPT been linked (6,16,17,20,21,25 (4); the position of MEN) was established from the deletion data shown in Fig. 1.…”

Section: Discussionmentioning

confidence: 99%

Localization of the MEN1 gene to a small region within chromosome 11q13 by deletion mapping in tumors.

Byström

Larsson

Blomberg

et al. 1990

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

267

123

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The gene for multiple endocrine neoplasia type 1 (MENi), an inherited predisposition to neuroendocrine neoplasm of the parathyroid glands, the pancreatic islet parenchyma, and the anterior pituitary gland, was recently mapped to chromosome 11q13 based on genetic linkage in families. We now show that the pathogenesis of MEN1-associated parathyroid lesions involves unmaking of a recessive mutation at the disease locus and that sporadic primary hyperparathyroidism shares the same mechanisms. MENi patients and from 24 patients with sporadic primary hyperparathyroidism were fresh-frozen and stored at -700C.The parathyroid lesions 11-3 LU-HPT and HPT-EZ were obtained from members of the LU and EZ kindreds (3). Specimens of insulinoma parenchyma from case II-1 of the LU kindred (3) were also included.Pituitary tumors from 27 cases, all but one (APA-23) with no signs of MEN1, were obtained by a trans-sphenoidal surgical approach and treated in the same manner. Four

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Section: Discussionmentioning

confidence: 99%

Localization of the MEN1 gene to a small region within chromosome 11q13 by deletion mapping in tumors.

Byström

Larsson

Blomberg

et al. 1990

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

267

123

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“…Southern blots were used to screen for gene deletions or rearrangements using cDNA and genomic probes derived from the retinoblastoma locus (Wiggs et al 1988). Intragenic RFLPs (Wiggs et al 1988;Toguchida et al 1993), were analyzed to determine the transmission of alleles in families and to determine whether an allele was lost in a tumor. In some cases, mutations beyond the resolution of Southern blot techniques were detected by single-strand conformation polymorphism (SSCP) analysis and direct genomic sequencing of the exons of the RB gene Hogg et al 1992;Shimizu et al 1994).…”

Section: Methodsmentioning

confidence: 99%

“…DNA was purified from leukocytes and in some cases tumor cells from patients with retinoblastoma and their relatives. Southern blots were used to screen for gene deletions or rearrangements using cDNA and genomic probes derived from the retinoblastoma locus (Wiggs et al 1988). Intragenic RFLPs (Wiggs et al 1988;Toguchida et al 1993), were analyzed to determine the transmission of alleles in families and to determine whether an allele was lost in a tumor.…”

Section: Methodsmentioning

confidence: 99%

Quantification of the paternal allele bias for new germline mutations in the retinoblastoma gene

1997

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New germline mutations in the human retinoblastoma gene are known to arise preferentially on paternally derived chromosomes, but the magnitude of that bias has not been measured. We evaluated 49 cases with a new germline mutation and found that in 40 cases (82%) the mutation arose on the paternally derived allele. We also evaluated 48 cases likely to have a somatic initial mutation; in this group the initial mutation arose on paternal or maternal chromosomes with approximately equal frequency. There was no statistically significant difference in the average age of fathers of children with new paternal germline mutations from the average age of fathers of children with new maternal germline mutations or somatic initial mutations. Combining the data with that from previous reports from other groups, the proportion of new germline mutations arising on a paternally derived allele is 85% (based on 72 cases; 95% confidence interval = 76-93%). This number can be useful in the genetic counseling of some families with retinoblastoma.

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“…It encodes a 110-kDa nuclear phosphoprotein (pRb) which participates in the transcriptional control mechanisms mediating progression through the G 1 phase of the cell cycle [10]. Germline mutations of the retinoblastoma gene in particular are predisposed to cause hereditary malignant eye tumors in children under 4 years of age [4,40]. Somatic point mutations have been detected throughout the Rb gene, with exons 3, 8, 18, and 19 preferably altered [10].…”

Section: Introductionmentioning

confidence: 98%

Loss of heterozygosity of the retinoblastoma gene is correlated with the altered pRb expression in human endometrial cancer

et al. 2002

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The retinoblastoma (Rb) gene was the first tumor suppressor gene to be discovered; however, data on the influence of Rb inactivation on endometrial carcinogenesis are scarce. We investigated 46 paired primary human endometrial carcinomas and normal tissues to assess the frequency of loss of heterozygosity (LOH) in Rb and 20 tumor pairs to detect the frequency of p53 LOH. Moreover, expression of the retinoblastoma protein (pRb) was assessed immunohistochemically. Of 44 informative cases 8 showed loss of one allele in at least one Rb marker; Rb LOH frequency thus reached 18%. Two omental metastases of endometrial origin showed a heterogeneity pattern similar to that of the primary tumors. We did not find a significant correlation between Rb LOH and patient age, clinical stage, histological grade or muscle invasion of the tumor. Nevertheless, Rb LOH was demonstrated at early (stage I, 5/27, 18%) and advanced (stages II-IV; 3/9, 33%) clinical stages of the neoplasm, suggesting that LOH at the Rb locus occurs before the clonal expansion of the tumor. There was a significant correlation between Rb LOH and weak/absent pRb expression. We noted a single case of p53 LOH at intron 1, but no tumor showed both alterations simultaneously. Our data suggest that LOH at the Rb locus plays a role in the oncogenesis of a subset of uterine neoplasms and corresponds with the altered expression of the pRb.

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Prediction of the risk of hereditary retinoblastoma, using DNA polymorphisms within the retinoblastoma gene

Cited by 16 publications

References 0 publications

Localization of the MEN1 gene to a small region within chromosome 11q13 by deletion mapping in tumors.

Localization of the MEN1 gene to a small region within chromosome 11q13 by deletion mapping in tumors.

Quantification of the paternal allele bias for new germline mutations in the retinoblastoma gene

Loss of heterozygosity of the retinoblastoma gene is correlated with the altered pRb expression in human endometrial cancer

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