title: Analysis of copy number changes on chromosome 16q in male breast cancer by multiplex ligation-dependent probe amplification.
abstract: Gene copy number changes have an important role in carcinogenesis and could serve as potential biomarkers for prognosis and targets for therapy. Copy number changes mapping to chromosome 16 have been reported to be the most frequent alteration observed in female breast cancer and a loss on 16q has been shown to be associated with low grade and better prognosis. In the present study, we aimed to characterize copy number changes on 16q in a group of 135 male breast cancers using a novel multiplex ligation-dependent probe amplification kit. One hundred and twelve out of 135 (83%) male breast cancer showed copy number changes of at least one gene on chromosome 16, with frequent loss of 16q (71/135; 53%), either partial (66/135; 49%) or whole arm loss (5/135; 4%). Losses on 16q were thereby less often seen in male breast cancer than previously described in female breast cancer. Loss on 16q was significantly correlated with favorable clinicopathological features such as negative lymph node status, small tumor size, and low grade. Copy number gain of almost all genes on the short arm was also significantly correlated with lymph node negative status. A combination of 16q loss and 16p gain correlated even stronger with negative lymph node status (n=112; P=0.012), which was also underlined by unsupervised clustering. In conclusion, copy number loss on 16q is less frequent in male breast cancer than in female breast cancer, providing further evidence that male breast cancer and female breast cancer are genetically different. Gain on 16p and loss of 16q identify a group of male breast cancer with low propensity to develop lymph node metastases.
authors.affiliation: Department of Pathology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Miangela M
authors.initials: MM
authors.lastname: Lacle
authors.forename: Robert
authors.initials: R
authors.lastname: Kornegoor
authors.forename: Cathy B
authors.initials: CB
authors.lastname: Moelans
authors.forename: Anoek H
authors.initials: AH
authors.lastname: Maes-Verschuur
authors.forename: Carmen
authors.initials: C
authors.lastname: van der Pol
authors.forename: Arjen J
authors.initials: AJ
authors.lastname: Witkamp
authors.forename: Elsken
authors.initials: E
authors.lastname: van der Wall
authors.forename: Josef
authors.initials: J
authors.lastname: Rueschoff
authors.forename: Horst
authors.initials: H
authors.lastname: Buerger
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018567:Breast Neoplasms, Male / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002885:Chromosomes, Human, Pair 16; D056915:DNA Copy Number Variations; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D060787:Neoplasm Grading; D009426:Netherlands; D010641:Phenotype; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011933:Reagent Kits, Diagnostic; D012307:Risk Factors; D013997:Time Factors; D047368:Tumor Burden
chemical_list: D011933:Reagent Kits, Diagnostic