Detailed deletion mapping in sporadic breast cancer at chromosomal region 17p13 distal to the TP53 gene: association with clinicopathological parameters.
Chromosome 17p is among the most frequently deleted regions in a variety of human malignancies including breast cancer. This study has further refined the localization of a putative tumour suppressor gene (TSG) at 17p13 distal to the TP53 gene in breast carcinomas. It was found that 73% (37 of 51) of the breast tumours exhibited loss of heterozygosity (LOH) at one or more loci at 17p13. The allelic loss patterns of these tumours suggest the presence of at least seven commonly deleted regions on 17p13. The three most frequently deleted regions were mapped at chromosomal location 17p13.3-17p13.2 between the markers D17S831 and D17S1845 (56% LOH), at 17p13.1 between D17S1810 and D17S1832 (53% LOH), and at 17p13.1 between D17S938 and TP53 (55% LOH). A significant correlation was found between loss at 17p13 and tumour grade, size, proliferative activity, and oestrogen receptor (ER) status. Losses at 17p13 were seen more frequently in large and poorly differentiated tumours with high proliferative activity. These data support and extend previous reports on the presence of a putative TSG(s) at chromosomal region 17p13 distal to the TP53 gene and show that different subsets of LOH are associated with more aggressive tumour behaviour.
Seitz
S
S
Department of Tumor Genetics, Max Delbrueck Center for Molecular Medicine, Robert Roessle Strasse 10, 13122 Berlin, Germany. sseitz@mdc-berlin.de
Poppe
K
K
Fischer
J
J
Nothnagel
A
A
Estévez-Schwarz
L
L
Haensch
W
W
Schlag
P M
PM
Scherneck
S
S
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics; D018275:Carcinoma, Lobular / Q000235:genetics; D018276:Carcinoma, Medullary / Q000235:genetics; D002291:Carcinoma, Papillary / Q000235:genetics; D002886:Chromosomes, Human, Pair 17; D005260:Female; D017353:Gene Deletion; D005819:Genetic Markers; D006801:Humans; D019394:Ki-67 Antigen; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D018709:Statistics, Nonparametric; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D005819:Genetic Markers; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53