Loss of heterozygosity at microsatellite markers from region p11-21 of chromosome 8 in microdissected breast tumor but not in peritumoral cells.
Alterations of chromosomal region 8p11-21 are very frequent in human cancers, and especially in breast cancer; yet, most of the genes involved have not been identified. We performed laser capture microdissection in a series of 52 consecutive breast tumor samples to obtain pure tumor cells without surrounding normal breast. To determine genomic subregions in which some of the cancer genes may be located, we conducted a search for loss of heterozygosity (LOH) at 13 microsatellite markers from this region. Two-thirds of the tumors showed LOH at least at one marker. Microdissection of pure tumor samples was helpful to precisely define four LOH subregions. No LOH was observed in the corresponding peritumoral tissues. We studied by immunohistochemistry (IHC) on tissue-microarrays the expression in the same tumors, of the protein product of three potential tumor genes lying close to or within the subregions of LOH. In most samples, the TACC1 gene product was downregulated in tumor cells as compared to normal cells. Our results show that the centromeric portion of chromosome arm 8p is frequently altered in breast tumor cells.
Charafe-Jauffret
Emmanuelle
E
Departement d'Oncologie Moleculaire, Institut Paoli-Calmettes (IPC), Marseille, France.
Moulin
Jean-François
JF
Ginestier
Christophe
C
Bechlian
Didier
D
Conte
Nathalie
N
Geneix
Jeannine
J
Adélaïde
José
J
Noguchi
Tetsuro
T
Hassoun
Jacques
J
Jacquemier
Jocelyne
J
Birnbaum
Daniel
D
D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8; D005260:Female; D005326:Fetal Proteins / Q000032:analysis; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008869:Microtubule-Associated Proteins / Q000032:analysis; D008875:Middle Aged; D020890:Neuregulin-1 / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis
D005326:Fetal Proteins; D005819:Genetic Markers; D008869:Microtubule-Associated Proteins; D020890:Neuregulin-1; D009687:Nuclear Proteins; C120584:TACC1 protein, human