Loss of heterozygosity for chromosome 11 in primary human breast tumors is associated with poor survival after metastasis.
A common feature of the malignant progression of human tumors is loss of heterozygosity (LOH) for various regions of their genomes. Such events encompassing chromosomes 11p15 and 11q23 are frequent in human breast tumors. Here, we have analyzed genetic and clinical characteristics of a series of primary breast tumors in order to determine: (a) a more finely mapped estimate of the involved regions; (b) whether there is a relationship in the presentation of LOH between the two regions; and (c) whether a correlation exists between such LOH and any of the clinical parameters pertaining to each patient. We found that LOH for 11p15.5 and 11q23 occurred in 35 and 46% of the 86 primary breast carcinomas, respectively, but in none of the 10 benign tumors examined. The minimal region of LOH for 11p15 was in the approximately 2-megabase region between loci TH and D11S988. Twenty-nine % of the tumors showed LOH simultaneously at both 11p15 and 11q23, 5% had LOH only at 11p15.5, and 15% had LOH only at 11q23. Among these genetic groups, clinical features such as tumor size, involvement of auxiliary nodes, histological subtype, tumor grade, estrogen/progesterone receptor status, and patient age were not markedly different. However, LOH of 11q23 (either alone or in conjunction with LOH of 11p15) in the primary tumor was found to be highly predictive of aggressive postmetastatic disease course with substantially reduced survival (P = 0.0004; log rank test). We also observed a slight trend toward a more rapid development of metastatic lesions, without obvious site specificity, in patients with primary tumors showing LOH for chromosome 11 in the pathogenesis of human breast cancer; we suggest that its effects are late in the progression of this disease.
Winqvist
R
R
Ludwig Institute for Cancer Research, La Jolla, CA 92093-0660, USA.
Hampton
G M
GM
Mannermaa
A
A
Blanco
G
G
Alavaikko
M
M
Kiviniemi
H
H
Taskinen
P J
PJ
Evans
G A
GA
Wright
F A
FA
Newsham
I
I
D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D004276:DNA, Satellite / Q000235:genetics; D005260:Female; D005348:Fibrocystic Breast Disease / Q000235:genetics / Q000473:pathology; D005500:Follow-Up Studies; D005819:Genetic Markers; D006801:Humans; D009362:Neoplasm Metastasis; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D011897:Random Allocation; D012091:Repetitive Sequences, Nucleic Acid; D016019:Survival Analysis; D013997:Time Factors
D004276:DNA, Satellite; D005819:Genetic Markers