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Definition of regions of the human genome affected by loss of heterozygosity in primary human breast tumors
Author(s) -
Callahan Robert,
Cropp Craig,
Sheng Zong Mei,
Merlo Giorgio,
Steeg Patricia,
Liscia Daniel,
Lidereau Rosette
Publication year - 1993
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240531131
Subject(s) - loss of heterozygosity , locus (genetics) , biology , genetics , gene , gene dosage , chromosome 17 (human) , chromosome , tumor suppressor gene , coding region , human genome , genome , microbiology and biotechnology , gene expression , allele , carcinogenesis
We have undertaken a systematic study of primary human breast tumor DNA to identify and characterize frequently occurring somatic mutations. Loss of heterozygosity (LOH) has been the most frequent mutation in our panels of primary breast tumor DNA. It is currently thought that LOH reveals recessive mutations within the affected region of the genome. One goal of our studies has been to physically define the target genes revealed by LOH in primary breast tumors. We have focused our efforts on chromosome 17, finding five regions of the chromosome which are independently affected by LOH in breast tumors. Two apparent target loci are on chromosome 17p; one is the TP53 gene. The other is an as‐yet undefined locus telomeric to the TP53 gene. Loss of expression of the nme 1 gene on chromosome 17q in tumors was linked to patients with a poor prognosis (p = 0.018). Although a significant trend (p = 0.05) was found between LOH of the nme 1 gene and loss of nme 1 expression, no point mutations were found within the coding region of the nme 1 gene by single strand conformational polymorphism (SSCP) or nucleotide sequence analysis. These and other results suggest to us that there may be potential tumor suppressor genes both centromeric and telomeric to the nme 1 locus on chromosome 17q.