ABSTRACT
Medullary thyroid carcinoma (MTC) occurs as a sporadic tumor or in connection with inherited cancer syndromes of multiple endocrine neoplasia type 2 and familial MTC. Missense RET proto-oncogene mutations and small in-frame deletions are found in most of the cases. In a significant amount of sporadic MTC cases somatic mutation at codon 918 (exon 16), or at codons 609, 611, 618, 620 (exon 10), or codons 630, 634 (exon 11) appear. We report here on three new somatic cell missense mutations of the RET proto-oncogene associated with sporadic MTC. In one tumor mutation at codon 922 TCC(Ser)-->TTC(Phe) in exon 16 was found. In another tumor two mutations at codons 639 GCA(Ala)-->GGA(Gly) and 641 GCT(Ala)-->CGT(Arg) in the exon 11 were observed. Allele-specific PCR followed by sequencing demonstrated the presence of both mutations at the same allele.
Subject(s)
Carcinoma, Medullary/genetics , Drosophila Proteins , Proto-Oncogene Proteins/genetics , Receptor Protein-Tyrosine Kinases/genetics , Thyroid Neoplasms/genetics , Base Sequence , Carcinoma, Medullary/pathology , DNA Mutational Analysis , DNA, Neoplasm/chemistry , DNA, Neoplasm/genetics , Humans , Mutation , Mutation, Missense , Polymorphism, Single-Stranded Conformational , Proto-Oncogene Mas , Proto-Oncogene Proteins c-ret , Thyroid Neoplasms/pathologyABSTRACT
Comparative allelotyping of the short arm of human chromosome 3 (3p) in four types of epithelial carcinomas was performed using an identical set of polymorphic markers. In total, 117 samples of non-papillary renal cell carcinoma (RCC), non-small cell lung carcinoma (NSCLC), carcinoma of uterine cervix (CC), and breast carcinoma (BC) were screened for loss of heterozygosity (LOH) with 10 di-, tri- and tetrameric markers covering nine bands of 3p. High LOH frequencies were detected in at least one locus: RCC (36/43, 84%), BC (20/26, 77%), NSCLC (16/24, 67%), and CC (15/24, 62%). Small interstitial deletions prevailed in BC and CC whereas large continuous and discontinuous deletions were mainly found in RCC and NSCLC. Different epithelial tumors displayed unique LOH profiles with partial overlaps in 3p26.1, 3p21.31, and 3p13. The overlap around D3S2409 (3p21.31) appeared common for RCC, BC and CC.
Subject(s)
Alleles , Biomarkers, Tumor , Carcinoma/genetics , Chromosomes, Human, Pair 3 , DNA, Neoplasm/genetics , Genetic Markers , DNA, Neoplasm/analysis , Humans , Loss of Heterozygosity , Polymorphism, GeneticSubject(s)
Gene Frequency , Genes, BRCA1/genetics , Mutation , Ovarian Neoplasms/genetics , Breast Neoplasms/epidemiology , Breast Neoplasms/genetics , Ethnicity/genetics , Female , Humans , Microsatellite Repeats , Middle Aged , Ovarian Neoplasms/epidemiology , Polymorphism, Single-Stranded Conformational , Russia/epidemiology , Sequence Analysis, DNAABSTRACT
Germ-line mutations of the BRCA1 gene are responsible for a substantial proportion of families with multiple cases of early-onset breast and/or ovarian cancer. Since the isolation of BRCA1 last year, >65 distinct mutations scattered throughout the coding region have been detected, making analysis of the gene time consuming and technically challenging. We have developed a multiplex heteroduplex analysis that is designed to analyze one-quarter of the coding sequence in a single-step screening procedure and that will detect approximately 50% of all BRCA1 mutations so far reported in breast/ovarian cancer families. We have used this technique to analyze BRCA1 in 162 families with a history of breast and/or ovarian cancer and identified 12 distinct mutations in 35 families.
