Loss of heterozygosity on chromosome 17p13 in breast carcinomas identifies tumors with high proliferation index.
The capacity of breast tumor cells to proliferate is considered a potential prognostic factor together with other histopathologic parameters. The authors determined the proliferation index on a large panel of human primary breast tumors by measuring the levels of incorporation of bromodeoxyuridine (BrdU) by fresh tumor specimens in culture. Previous analysis showed that the percentage of cells entering the S-phase of the cell cycle strongly correlates with tumor grade, tumor size, and estrogen and progesterone receptor status. The capacity of tumor cells to proliferate might be associated with specific genetic mutations in primary tumors. To test this hypothesis, a panel of 96 human breast carcinomas, for which the BrdU labeling index (LI) was known, were tested for loss of heterozygosity (LOH) or increased copy number (ICN) at chromosomes 1q, 3p, 13q, 17p, and 18q. On chromosome 17p, LOH and ICN were observed in 27% and 12%, respectively, of the informative breast tumors. The LOH on chromosome 17p was significantly associated with tumors having an elevated BrdU proliferation index (P = 0.022). No association (P = 0.45) was observed between BrdU LI and tumor size (T2 + T3 compared with T1), tumor grade, and lymph node status. Increased copy number on chromosome 17p, LOH or ICN on 1q, and LOH on 13q14, 18q, and 3p also showed no significant correlation with cell kinetic parameters. These data are consistent with the presence of a gene or genes on chromosome 17p13 near the YNZ22.1 locus whose normal functioning is necessary for controlling breast tumor cells proliferation in vivo.
Merlo
G R
GR
Oncogenetic Section, National Institutes of Health, Bethesda, Maryland.
Venesio
T
T
Bernardi
A
A
Canale
L
L
Gaglia
P
P
Lauro
D
D
Cappa
A P
AP
Callahan
R
R
Liscia
D S
DS
D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology*; D002886:Chromosomes, Human, Pair 17; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008940:Mitotic Index; D013936:Thymidine / Q000378:metabolism
D004273:DNA, Neoplasm; D001973:Bromodeoxyuridine; D013936:Thymidine