Relaxation of imprinting of human insulin-like growth factor II gene, IGF2, in sporadic breast carcinomas.
Breast cancer is the most frequent malignancy in women and genetically heterogeneous, and a variety of genetic lesions have been identified that tend to accumulate during the disease progress. In breast cancer, loss of heterozygosity (LOH) has been described in the critical regions of chromosomes 11p15 and 11q22-23. Genomic imprinting is defined as gamete specific modification causing differential expression of the two alleles of a gene, in somatic cells. Human insulin like growth factor II gene (IGF2), located on chromosome 11p15, the same region on which LOH frequently occurred in breast cancer, has been recently identified as a genomic imprinting gene expressing preferentially paternal allele. To determine whether loss of IGF2 imprinting was common in breast cancer we studied 30 patients with sporadic breast carcinoma. A new strategy for detecting intragenic Apa I polymorphism in the exon of IGF2 was used to examine allele-specific expression in the breast cancer specimens by reverse-transcription polymerase chain reaction (RT-PCR). Forty percent (12/30) of the breast cancer samples were identified as heterozygous for IGF2 and studied further. Nine of the 12 heterozygous patients showed biallelic expression of IGF2 by cDNA-PCR, indicating relaxation of normal imprinting at this chromosomal locus. Conclusively, aberrant imprinting of IGF2 in 30% of the breast cancer patients tested provides strong evidence that pathological loss or relaxation of IGF2 imprinting plays an important role in either tumorigenesis or cytokine dysregulation for breast cancer cells.
Wu
H K
HK
Department of Cellular and Molecular Pathology, Hospital for Sick Children, Toronto, Ontario, Canada.
Squire
J A
JA
Catzavelos
C G
CG
Weksberg
R
R
D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002880:Chromosomes, Human, Pair 11; D018076:DNA, Complementary / Q000235:genetics; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D005260:Female; D018392:Genomic Imprinting; D006579:Heterozygote; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D018076:DNA, Complementary; D007335:Insulin-Like Growth Factor II; D015252:Deoxyribonucleases, Type II Site-Specific; C032229:GANTC-specific type II deoxyribonucleases