Showing papers by "Michael R. Stratton published in 2001"
[...]
TL;DR: This experiment underscores the limited amount and variable quality of DNA sequence from cancer cells that is currently available and assessed whether it was possible to search directly for oncogenic sequence changes in cancer cells by comparing cancer genome sequences against the draft genome.
Abstract: Identification of the genes that cause oncogenesis is a central aim of cancer research. We searched the proteins predicted from the draft human genome sequence for paralogues of known tumour suppressor genes, but no novel genes were identified. We then assessed whether it was possible to search directly for oncogenic sequence changes in cancer cells by comparing cancer genome sequences against the draft genome. Apparently chimaeric transcripts (from oncogenic fusion genes generated by chromosomal translocations, the ends of which mapped to different genomic locations) were detected to the same degree in both normal and neoplastic tissues, indicating a significant level of false positives. Our experiment underscores the limited amount and variable quality of DNA sequence from cancer cells that is currently available.
153 citations
TL;DR: It is suggested that at least half of breast/ovarian families evaluated in a high-risk cancer evaluation clinic may have germline mutations in BRCA1 or BRC2, and whether the remaining families have mutations in noncoding regions in B RCA1, mutations in other, as-yet-unidentified, low-penetrance susceptibility genes, or represent chance clustering remains to be determined.
Abstract: PURPOSE: Data from the Breast Cancer Linkage Consortium suggest that the proportion of familial breast and ovarian cancers linked to BRCA1 or BRCA2 may be as high as 98% depending on the characteristics of the families, suggesting that mutations in BRCA1 or BRCA2 may entirely account for hereditary breast and ovarian cancer families. We sought to determine what proportion of families with both breast and ovarian cancers seen in a breast cancer risk evaluation clinic are accounted for by coding region germline mutations in BRCA1 and BRCA2 as compared to a linkage study group. We also evaluated what clinical parameters were predictive of mutation status. PATIENTS AND METHODS: Affected women from 100 families with at least one case of breast cancer and at least one case of ovarian cancer in the same lineage were screened for germline mutations in the entire coding regions of BRCA1 and BRCA2 by conformation-sensitive gel electrophoresis, apolymerase chain reaction–based heteroduplex analysis, or direct sequen...
82 citations
TL;DR: To evaluate the roles of MNG1, TCO1, fPTC, PTEN, TSHR, and TRKA in familial nonmedullary thyroid cancer, a comprehensive mutation and linkage analysis of these genes in 22 families was carried out.
Abstract: About 5% of nonmedullary thyroid cancer is familial These familial nonmedullary thyroid cancer cases are characterized by an earlier age of onset, more aggressive phenotype, and in some families a high propensity to benign thyroid disease Little is known about the genes conferring predisposition to nonmedullary thyroid cancer Three loci have been identified through genetic linkage: MNG1 on 14q32, TCO1 on 19p132, and fPTC on 1p21 In addition to these putative genes, a number of loci represent candidate familial nonmedullary thyroid cancer predisposition genes by virtue of their involvement in sporadic disease (TRKA), their role in benign disease (TSHR), and because they underlie syndromes with a risk of nonmedullary thyroid cancer (PTEN) To evaluate the roles of MNG1, TCO1, fPTC, PTEN, TSHR, and TRKA in familial nonmedullary thyroid cancer, we have carried out a comprehensive mutation and linkage analysis of these genes in 22 families One family was linked to chromosome 19q132, confirming that TCO1 underlies a subset of familial nonmedullary thyroid cancer None of the families was linked to MNG1 or fPTC, and there was no evidence to support the roles of PTEN, TSHR, or TRKA Familial nonmedullary thyroid cancer is an emerging clinical phenotype that is genetically heterogeneous, and none of the currently identified genes accounts for the majority of families
69 citations
TL;DR: Examining a series of 71 LCIS patients for germline MSH2 and MLH1 mutations suggests that mutations in MLH 1 may underlie a subset of LCIS cases.
16 citations
TL;DR: To determine whether a WT predisposition locus exists at 12q the authors examined the region in two familial Wilms tumor pedigrees unlinked to the known FWT genes on chromosomes 17q, 19q, and 11p, and in both families WT did not segregate with chromosome 12q markers located within the deletion boundaries.
Abstract: A 14-month-old boy presenting with Wilms tumor (WT) was found to have a small de novo deletion of the long arm of chromosome 12 (12q11-12q13.11). Microsatellite analysis of this region from constitutional DNA showed that the paternal allele was absent between the markers D12S331 and D12S1713 (inclusive). In the WT there was no evidence of loss of the maternal chromosome. Constitutional chromosome abnormalities can often point to the presence of genes that are important in disease, and the deletion of chromosome 12 in this patient may indicate a gene involved in WT. To determine whether a WT predisposition locus exists at 12q we examined the region in two familial Wilms tumor (FWT) pedigrees unlinked to the known FWT genes on chromosomes 17q (FWT1), 19q (FWT2), and 11p (WT1). In both families WT did not segregate with chromosome 12q markers located within the deletion boundaries.
14 citations