Genetic alterations of the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q in human breast carcinomas.
Fifty-nine primary breast carcinomas and 11 metastases were examined to identify genetic alterations in the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q. Loss of heterozygosity (LOH) was frequently observed on chromosome arms 17p (p144D6 lost in 75%, pYNZ22.1 in 55%, and TP53 in 48% of the primary tumours), 13q (RBI lost in 40% of the primary tumours), and 17q (pRMU3 lost in 35%, pTHH59 in 29%, and NM23HI in 26% of the primary tumours). Loss of all the markers except p144D6 was observed even more frequently in the metastases. Pairwise comparisons for concordance of allele losses on 17p indicated that there might be two genes on 17p implicated in breast cancer development; the TP53 gene and a gene located close to the p144D6 and pYNZ22.1 markers. LOH of the RBI gene was associated with LOH of pYNZ22.1 and p144D6, but not with LOH of TP53. LOH of RBI and TP53 was associated with occurrence of ductal carcinomas, RBI and p144D6 losses with tumour size, and p144D6 losses with positive node status as well. LOH of TP53 and the three 17q markers NM23HI, pTHH59, and pRMU3 was most frequently observed in tumours from postmenopausal women. p144D6 losses occurred most frequently in progesterone receptor-negative tumours, whereas pTHH59 losses occurred most frequently in oestrogen receptor-negative tumours. LOH of the investigated loci was not associated with ERBB2 protooncogene amplification, with positive family history of breast cancer, or with survival.
Department of Genetics, Norwegian Radium Hospital, Montebello, Oslo.
T I
TI
Andersen
A
A
Gaustad
L
L
Ottestad
G W
GW
Farrants
J M
JM
Nesland
K M
KM
Tveit
A L
AL
Børresen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11; D002882:Chromosomes, Human, Pair 13; D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D005260:Female; D005784:Gene Amplification; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics; D009664:Norway; D011518:Proto-Oncogene Proteins / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases; D015996:Survival Rate
D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases