title: Chromosomal region 15q21.1 is a frequent target of allelic imbalance in advanced breast carcinomas.
abstract: Allelic imbalance constitutes a major mechanism of genetic aberrations in breast cancer and strongly indicates the involvement of tumor associated genes in the affected chromosomal regions. Preliminary results from our study indicated the existence of a tumor suppressor gene located on chromosomal arm 15q which may be involved in breast cancer progression.1 In the present study, 210 primary breast carcinomas, 30 metastases and 26 local recurrences from primary breast carcinomas have been analyzed with a panel of 18 highly polymorphic microsatellite markers spanning the chromosomal region 15q11-21.3. Allelic imbalance at 15q with at least 1 marker was seen in 36 of 56 (64.3%) metastases and recurrences, but only in 58 of 210 (27.6%) primary tumors (p<0.0001). We identified a subregion defined by microsatellite marker CYP19 (15q21.1) that showed significantly higher frequencies of allelic imbalance in metastases and recurrences (57.6%) when compared to primary carcinomas (8.9%; p<0.0001). Allelic imbalance at 15q was correlated with histopathologic parameters of the patients with primary breast carcinomas. We detected a significant association with established predictors of poor prognosis, i.e., negative estrogen receptor status (p=0.003), negative progesterone receptor status (p=0.028), high grade (p=0.014) and positive axillary lymph nodes (p=0.013). In summary, our data provide further evidence for a novel prognostic marker in breast carcinomas located in the chromosomal region 15q21.
authors.affiliation: Department of Obstetrics and Gynecology, Medical Center, University of Bonn, Bonn, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Rhiem
authors.forename: Annette
authors.initials: A
authors.lastname: Klein
authors.forename: Miriam
authors.initials: M
authors.lastname: Münch
authors.forename: Rene
authors.initials: R
authors.lastname: Kreutzfeld
authors.forename: Juliane
authors.initials: J
authors.lastname: Ramser
authors.forename: Eva
authors.initials: E
authors.lastname: Wardelmann
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schackert
authors.forename: Andreas
authors.initials: A
authors.lastname: Von Deimling
authors.forename: Otmar D
authors.initials: OD
authors.lastname: Wiestler
authors.forename: Rita K
authors.initials: RK
authors.lastname: Schmutzler
mesh_terms: D000483:Alleles; D022981:Allelic Imbalance; D001141:Aromatase / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics*; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D004260:DNA Repair; D018450:Disease Progression; D005260:Female; D005819:Genetic Markers; D006801:Humans; D018895:Microsatellite Repeats; D009362:Neoplasm Metastasis; D011110:Polymorphism, Genetic; D011379:Prognosis; D014407:Tumor Cells, Cultured
chemical_list: D005819:Genetic Markers; D001141:Aromatase