title: Absence of cyclin D1/PRAD1 point mutations in human breast cancers and parathyroid adenomas and identification of a new cyclin D1 gene polymorphism.
abstract: PRAD1 (cyclin D1) has been implicated in the molecular pathogenesis of a variety of tumors, including parathyroid adenomas, t(11;14)-bearing B-lymphoid tumors, and breast cancer. The sequence of the overexpressed PRAD1 genes has been directly analyzed in only two tumor specimens, a benign parathyroid adenoma and a malignant centrocytic lymphoma. Thus, little is known about PRAD1 sequence in the vast majority of human primary tumors, including breast cancers. Using single-strand conformational polymorphism (SSCP) analysis, we have examined the coding region of the PRAD1 gene in 30 primary breast cancers and 25 parathyroid adenomas. Polymerase chain reaction (PCR)-SSCP analysis of the coding region of exons 1-5 of the PRAD1 gene did not reveal any tumor-specific mutations. During the course of screening for mutations, we found and established the sequence variants of a new DNA polymorphism at codon 241 within exon 4 of the PRAD1 gene. Since this polymorphism is located within the coding region of the PRAD1 gene, it will allow determination of allele-specific expression of the gene and the detection of allele imbalance. At least in breast and parathyroid neoplasms, overexpression of the wild-type PRAD1 sequence, rather than point mutational activation, appears to be the predominant mechanism by which PRAD1 exerts its oncogenic action.
authors.affiliation: Laboratory of Endocrine Oncology, Jackson, Massachusetts General Hospital, Boston 02114, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Hosokawa
authors.forename: T
authors.initials: T
authors.lastname: Tu
authors.forename: H
authors.initials: H
authors.lastname: Tahara
authors.forename: A P
authors.initials: AP
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: Arnold
mesh_terms: D000236:Adenoma / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D019938:Cyclin D1; D016213:Cyclins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D015513:Oncogene Proteins / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics*; D010282:Parathyroid Neoplasms / Q000235:genetics*; D017354:Point Mutation; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D016213:Cyclins; D015345:Oligonucleotide Probes; D015513:Oncogene Proteins; D019938:Cyclin D1