title: MYEOV: a candidate gene for DNA amplification events occurring centromeric to CCND1 in breast cancer.
abstract: Rearrangements of chromosome 11q13 are frequently observed in human cancer. The 11q13 region harbors several chromosomal breakpoint clusters found in hematologic malignancies and exhibits frequent DNA amplification in carcinomas. DNA amplification patterns in breast tumors are consistent with the existence of at least 4 individual amplification units, suggesting the activation of more than 1 gene in this region. Two candidate oncogenes have been identified, CCND1 and EMS1/CORTACTIN, representing centrally localized amplification units. Genes involved in the proximal and distal amplicons remain to be identified. Recently we reported on a putative transforming gene, MYEOV, mapping 360 kb centromeric to CCND1. This gene was found to be rearranged and activated concomitantly with CCND1 in a subset of t(11;14)(q13;q32)-positive multiple myeloma (MM) cell lines. To evaluate the role of the MYEOV gene in the proximal amplification core, we tested 946 breast tumors for copy number increase of MYEOV relative to neighboring genes or markers. RNA expression levels were studied in a subset of 72 tumors for which both RNA and DNA were available. Data presented here show that the MYEOV gene is amplified in 9.5% (90/946) and abnormally expressed in 16.6% (12/72) of breast tumors. Amplification patterns showed that MYEOV was most frequently coamplified with CCND1 (74/90), although independent amplification of MYEOV could also be detected (16/90). Abnormal expression levels correlated only partially with DNA amplification. MYEOV DNA amplification correlated with estrogen and progesterone receptor-positive cancer, invasive lobular carcinoma type and axillary nodal involvement. In contrast to CCND1 amplification, no association with disease outcome could be found. Our data suggest that MYEOV is a candidate oncogene activated in the amplification core located proximal to CCND1.
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Heidelberg, Heidelberg, Germany.
authors.forename: Johannes W G
authors.initials: JW
authors.lastname: Janssen
authors.forename: Marguerite
authors.initials: M
authors.lastname: Cuny
authors.forename: Béatrice
authors.initials: B
authors.lastname: Orsetti
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodriguez
authors.forename: Hélène
authors.initials: H
authors.lastname: Vallés
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.forename: Ed
authors.initials: E
authors.lastname: Schuuring
authors.forename: Charles
authors.initials: C
authors.lastname: Theillet
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002503:Centromere / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D019938:Cyclin D1 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015513:Oncogene Proteins / Q000235:genetics*; D009857:Oncogenes; D011379:Prognosis; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm / Q000032:analysis; D014407:Tumor Cells, Cultured
chemical_list: C407245:MYEOV protein, human; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D019938:Cyclin D1