Chromosome I alterations in breast cancer: Allelic loss on Ip and Iq Is related to lymphogenic metastases and poor prognosis
✍ Scribed by Åke Borg; Qiu-Xia Zhang; Håkan Olsson; Eva Wenngren
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- English
- Weight
- 960 KB
- Volume
- 5
- Category
- Article
- ISSN
- 1045-2257
No coin nor oath required. For personal study only.
✦ Synopsis
The development of human breast cancer is characterized by a variety of genetic alterations, and cytogenetic analyses have documented the consistent involvement of both arms of chromosome I. In the present study, molecular markers detecting restriction fragment length polymorphisms were used in pairwise screening of normal and tumor DNA t o determine the frequency of allelic imbalance in breast tumors. Loss of heterozygosity (LOH) in the polymorphic epithelial mucin (PEM o r MUCI) gene at I q2 I was found in 16% of 89 informative (constitutionally heterozygous) cases, whereas gain in intensity of one allelic band was more frequent (37%), a total of 47% of cases manifesting either allelic loss or gain. Three additional tumors manifested a structural alteration. Allelic loss or gain in the PEM gene was not associated with other prognostic factors, e.g., tumor size, lymph node status, steroid receptors, D N A ploidy, S phase fraction, protooncogene amplification, histological type, o r patient age. However, LOH in the PEM gene was significantly correlated with early disease recurrence (P = 0.006). LOH on I p was found in 27% of I I 7 informative cases, using probes for either D IS57 o r D I Z 2 located at I p33-p35 and I p36, respectively. Somatic allelic imbalance on I p and I q seemed t o be independent events and not the effect of loss of a whole chromosome I. LOH on I p was significantly correlated t o the presence of lymph node metastasis, t o larger tumor size, and t o D N A nondiploidy, but no correlation was found t o disease outcome at this limited duration of follow-up (median 29 months). Genes Chrom Cancer 9 3 I 1-320 ( I 992). 0 1992 Wiley-Liss. Inc