title: Clonal heterogeneity of lymphoid malignancies correlates with poor prognosis.
abstract: Clonal heterogeneity in lymphoid malignancies has been recently reported in adult T-cell lymphoma/leukemia, peripheral T-cell lymphoma, not otherwise specified, and mantle cell lymphoma. Our analysis was extended to other types of lymphoma including marginal zone lymphoma, follicular lymphoma and diffuse large B-cell lymphoma. To determine the presence of clonal heterogeneity, 332 cases were examined using array comparative genomic hybridization analysis. Results showed that incidence of clonal heterogeneity varied from 25% to 69% among different types of lymphoma. Survival analysis revealed that mantle cell lymphoma and diffuse large B-cell lymphoma with clonal heterogeneity showed significantly poorer prognosis, and that clonal heterogeneity was confirmed as an independent predictor of poor prognosis for both types of lymphoma. Interestingly, 8q24.1 (MYC) gain, 9p21.3 (CDKN2A/2B) loss and 17p13 (TP53, ATP1B2, SAT2, SHBG) loss were recurrent genomic lesions among various types of lymphoma with clonal heterogeneity, suggesting at least in part that alterations of these genes may play a role in clonal heterogeneity.
authors.affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Suguro
authors.forename: Noriaki
authors.initials: N
authors.lastname: Yoshida
authors.forename: Akira
authors.initials: A
authors.lastname: Umino
authors.forename: Harumi
authors.initials: H
authors.lastname: Kato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tagawa
authors.forename: Masao
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Noriko
authors.initials: N
authors.lastname: Fukuhara
authors.forename: Sivasundaram
authors.initials: S
authors.lastname: Karnan
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takeuchi
authors.forename: Toby D
authors.initials: TD
authors.lastname: Hocking
authors.forename: Kotaro
authors.initials: K
authors.lastname: Arita
authors.forename: Kennosuke
authors.initials: K
authors.lastname: Karube
authors.forename: Shinobu
authors.initials: S
authors.lastname: Tsuzuki
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Masao
authors.initials: M
authors.lastname: Seto
mesh_terms: D002051:Burkitt Lymphoma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002898:Chromosomes, Human, Pair 8; D055028:Comparative Genomic Hybridization; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D017353:Gene Deletion; D018628:Gene Dosage; D006801:Humans; D008223:Lymphoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology*; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008224:Lymphoma, Follicular / Q000235:genetics / Q000401:mortality / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000401:mortality / Q000473:pathology; D011379:Prognosis
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: Array comparative genomic hybridization; heterogeneity; malignant lymphoma; patient outcome assessment; tumor cell population