title: Analysis of ALK gene in 133 patients with breast cancer revealed polysomy of chromosome 2 and no ALK amplification.
abstract: ALK has emerged as a novel tumorigenic factor in several epithelial human cancers. Crizotinib, an ALK tyrosine kinase inhibitor, is currently approved to treat lung cancer patients exhibiting ALK gene rearrangements. Our goal was to determine the incidence of ALK aberrations in relation to different breast cancer types. Tissue micro-arrays were constructed of ER+/PR±/HER2- (n = 37), ER-/PR-/HER2+ (n = 15), ER-/PR-/HER2- (n = 61) and ER+/PR+/HER2+ (n = 20) breast cancers; including 13 inflammatory breast carcinomas. FISH was performed using ALK break-apart and chromosome 2 centromere enumeration probes (CEP2). Neither ALK rearrangements nor amplification were identified in the 133 breast cancer cases evaluated. However, copy number gains (CNG) of ALK were identified in 82 of 133 patients (62 %). The CEP2 analysis revealed polysomy of chromosome 2 in all HCNG and LCNG cases, indicating the CNG of ALK are due to polysomy of chromosome 2, rather than true amplification of ALK. To conclude, we observed CNG of ALK secondary to chromosome 2 polysomy in a significant percentage of breast cancer cases, a phenomenon similar to polysomy 17. This study is one of the largest studies to have investigated ALK aberrations in breast cancer and the only study to include all subtypes.
authors: Department of Pathology and Laboratory Medicine, The Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1194, New York, NY 10029 USA.
authors: Matthew G
authors: MG
authors: Hanna
authors: Department of Pathology and Laboratory Medicine, The Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1194, New York, NY 10029 USA.
authors: Vesna
authors: V
authors: Najfeld
authors: Department of Oncological Sciences, The Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, NY USA.
authors: Hanna Y
authors: HY
authors: Irie
authors: Department of Pathology and Laboratory Medicine, The Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1194, New York, NY 10029 USA.
authors: Joseph
authors: J
authors: Tripodi
authors: Department of Pathology and Laboratory Medicine, The Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1194, New York, NY 10029 USA.
authors: Anupma
authors: A
authors: Nayak
keywords: ALK; Breast cancer; FISH; Inflammatory; Polysomy; TMA