Coamplification in tumors of KRAS2, type 2 inositol 1,4,5 triphosphate receptor gene, and a novel human gene, KRAG.
Heighway, Jim Betticher, Daniel C Hoban, Paul R Altermatt, H J Cowen, Rachel L
Heighway, Jim
Betticher, Daniel C
Hoban, Paul R
Altermatt, H J
Cowen, Rachel L
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Abstract
Analysis of a region of DNA, coamplified in tumors with KRAS2, resulted in the identification of the human homologue of the mouse KRAG gene. The gene was widely expressed in a range of cell lines, tumors, and normal tissue and demonstrated a high degree of alternate splicing. A human KRAG cDNA sequence, with a structure similar to that encoded by the amplified gene in mouse Y1 adrenal carcinoma cells, was isolated by RT-PCR. The predicted amino acid similarity between the two sequences was 91%, and hydrophobicity plots suggested a structure closely resembling that of transmembrane 4 superfamily members. Identification of a PCR-based restriction fragment length polymorphism confirmed biallelic expression of KRAG but suggested allele-specific splicing differences in tumors. Northern analysis of mRNA derived from a range of tissues suggested high level expression in muscle and confirmed alternate splicing. To facilitate the analysis of exon junctions, a YAC clone encoding the genomic sequence was identified. This allowed the localization of KRAG to human chromosome 12p11.2. Isolation of one end of this nonchimeric clone demonstrated a perfect match with a 247-bp sequence within the 3' untranslated region of the type 2 1,4, 5-inositol triphosphate receptor gene. Multiplex PCR confirmed the inclusion of both genes in the KRAS2 amplicon in human malignancy, suggesting that either may contribute to the malignant phenotype.
Description
Date
1996-07-01
Publisher
Collections
Keywords
Cancer
Cancer DNA
Cancer Proteins
Cancer RNA
Lung Cancer
Cultured Tumour Cells
Cancer DNA
Cancer Proteins
Cancer RNA
Lung Cancer
Cultured Tumour Cells
Type
Article
Citation
Coamplification in tumors of KRAS2, type 2 inositol 1,4,5 triphosphate receptor gene, and a novel human gene, KRAG. 1996, 35 (1):207-14 Genomics