Different mechanisms of chromosome 16 loss of heterozygosity in well- versus poorly differentiated ductal breast cancer.
Loss of heterozygosity (LOH) at the long arm of chromosome 16 is a frequent genetic alteration in breast cancer. It can occur by physical loss of part of or the entire chromosomal arm, resulting in a decrease in copy number or loss followed by mitotic recombination. Comparative genomic hybridization (CGH) demonstrated that well-differentiated breast tumors showed significantly more physical loss of 16q than did poorly differentiated ones and that this difference was already discernable in the preinvasive stage. However, polymorphic markers detected no difference in the frequency of 16q LOH between invasive tumors of different histological grade. Here, by combining data on LOH (n=52), fluorescence in situ hybridization (n=18) with chromosome 16-specific probes, and CGH (n=34), we show a preference in well-differentiated grade I tumors for physical loss of chromosome arm 16q, whereas in poorly differentiated grade III tumors LOH is accompanied by mitotic recombination. This clarifies the discrepancies observed between CGH and LOH for 16q in breast cancer. These different somatic genetic mechanisms may reflect the presence of multiple tumor suppressor genes that are the target of LOH at chromosome arm 16q.
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. A.M.Cleton-Jansen@lumc.nl
Anne-Marie
AM
Cleton-Jansen
Horst
H
Buerger
Natalja ter
Nt
Haar
Katja
K
Philippo
Marc J
MJ
van de Vijver
Werner
W
Boecker
Vincent T H B M
VT
Smit
Cees J
CJ
Cornelisse
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D044584:Carcinoma, Ductal / Q000235:genetics* / Q000473:pathology; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D011003:Ploidies
D005819:Genetic Markers