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Biomedical subjects

R White

Publications and source records attributed to R White.

At least 379 records · Page 21Linked to original sources
PubMed1989

Specific genetic change in tumors associated with von Hippel-Lindau disease.

Previous reports showed that the loss of DNA sequences on the short arm of chromosome 3 (3p) is consistently found in sporadic renal cell carcinomas. To evaluate the significance of this genetic change, we looked for the loss of 3p alleles in hereditary renal cell carcinomas and other tumors from patients with von Hippel-Lindau disease. Specific loss of alleles from chromosome 3p was detected with polymorphic DNA markers in 11 renal cell carcinomas, one pheochromocytoma, two spinal hemangioblastomas and one cerebellar hemangioblastoma from von Hippel-Lindau patients. Multiple renal cell carcinomas in individuals with von Hippel-Lindau disease showed loss of the same chromosome 3p alleles, which demonstrated that the same chromosome was deleted in each tumor. Analysis of haplotypes indicated that the loss of chromosome 3p alleles was from the chromosome bearing the balancing, wild-type allele of the VHL gene. These results are consistent with the concept that the VHL gene is a recessive oncogene. Renal cell carcinoma, pheochromocytoma, and spinal and cerebellar hemangioblastomas develop in predisposed family members when somatic mutational events lead to loss of chromosome 3p sequences bearing the wild-type allele of the VHL gene.

Alleles↗
PubMed1989

Clinical and pathological associations with allelic loss in colorectal carcinoma [corrected].

Clinical and pathological associations with molecular genetic alterations were studied in colorectal carcinomas from 83 patients. Fractional allelic loss, a measure of allelic deletions throughout the genome, and allelic deletions of specific chromosomal arms (the short arm of 17 and long arm of 18) each provided independent prognostic information by multivariate analysis when considered individually with Dukes' classification. Distant metastasis was significantly associated with high fractional allelic loss and with deletions of 17p and 18q. Mutations of ras proto-oncogenes and deletions of 5q had no prognostic importance. Statistically significant associations were also found between allelic losses and a family history of cancer, left-sided tumor location, and absence of extracellular tumor mucin. Allelic deletion analysis thus identified subsets of colorectal carcinoma with increased predilection for distant metastasis and cancer-related death. Further studies may define a subset of genetic alterations that can be used clinically to help assess prognosis.

Adult↗
PubMed1989

Two NF1 translocations map within a 600-kilobase segment of 17q11.2.

Balanced translocations, each involving chromosome 17q11.2, have been described in two patients with von Recklinghausen neurofibromatosis (NF1). To better localize the end points of these translocation events, and the NF1 gene (NF1) itself, human cosmids were isolated and mapped in the immediate vicinity of NF1. One cosmid probe, c11-1F10, demonstrated that both translocation breakpoints, and presumably NF1, are contained within a 600-kilobase Nru I fragment.

Animals↗
PubMed1989

Allelotype of colorectal carcinomas.

To examine the extent and variation of allelic loss in a common adult tumor, polymorphic DNA markers were studied from every nonacrocentric autosomal arm in 56 paired colorectal carcinoma and adjacent normal colonic mucosa specimens. This analysis was termed an allelotype, in analogy with a karyotype. Three major conclusions were drawn from this analysis: (i) Allelic deletions were remarkably common; one of the alleles of each polymorphic marker tested was lost in at least some tumors, and some tumors lost more than half of their parental alleles. (ii) In addition to allelic deletions, new DNA fragments not present in normal tissue were identified in five carcinomas; these new fragments contained repeated sequences of the variable number of tandem repeat type. (iii) Patients with more than the median percentage of allelic deletions had a considerably worse prognosis than did the other patients, although the size and stage of the primary tumors were very similar in the two groups. In addition to its implications concerning the genetic events underlying tumorigenesis, tumor allelotype may provide a molecular tool for improved estimation of prognosis in patients with colorectal cancer.

Alleles↗
PubMed1989

Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas.

Previous studies have demonstrated that allelic deletions of the short arm of chromosome 17 occur in over 75% of colorectal carcinomas. Twenty chromosome 17p markers were used to localize the common region of deletion in these tumors to a region contained within bands 17p12 to 17p13.3. This region contains the gene for the transformation-associated protein p53. Southern and Northern blot hybridization experiments provided no evidence for gross alterations of the p53 gene or surrounding sequences. As a more rigorous test of the possibility that p53 was a target of the deletions, the p53 coding regions from two tumors were analyzed; these two tumors, like most colorectal carcinomas, had allelic deletions of chromosome 17p and expressed considerable amounts of p53 messenger RNA from the remaining allele. The remaining p53 allele was mutated in both tumors, with an alanine substituted for valine at codon 143 of one tumor and a histidine substituted for arginine at codon 175 of the second tumor. Both mutations occurred in a highly conserved region of the p53 gene that was previously found to be mutated in murine p53 oncogenes. The data suggest that p53 gene mutations may be involved in colorectal neoplasia, perhaps through inactivation of a tumor suppressor function of the wild-type p53 gene.

Alleles↗
PubMed1989

Benign familial neonatal convulsions linked to genetic markers on chromosome 20.

Recurrent seizures, commonly known as epilepsies, occur in 1.7% of the general population by age 40. The factors that initiate or underlie seizures are not well understood, but trauma, infectious disease and genetics have been implicated. An understanding of the molecular basis of seizures would shed light on the basic mechanisms of neuronal homeostasis and allow new therapeutic strategies to be explored. Here, we report the mapping of an epilepsy gene to a specific chromosomal region, on the basis of cosegregation of two closely-linked DNA markers with a form of epilepsy known as benign familial neonatal convulsions (BFNC2, 12120 in ref. 3). The linked markers confirm the genetic basis and autosomal dominant inheritance of this trait, and localize the gene causing BFNC in this family to the long arm of chromosome 20. This regional placement is the first step towards the isolation of a gene involved in neuronal activity in the human brain.

Chromosome Mapping↗
PubMed1989

Human type II collagen gene (COL2A1) assigned to chromosome 12q13.1-q13.2 by in situ hybridization with biotinylated DNA probe.

We have made a regional assignment of the type II collagen gene (COL2A1) on human chromosome 12 by means of an in situ hybridization technique with a biotinylated DNA probe. The precise localization of the signal was mapped to the band 12q13.1-q13.2. This result was in agreement with the previous mapping by isotopic in situ hybridization technique (12q13.1-q13.2), but not with the result of Southern hybridization analysis using somatic cell hybrids (12q14.3).

Chromosome Banding↗