title: Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers.
abstract: Highly rearranged and mutated cancer genomes present major challenges in the identification of pathogenetic events driving the neoplastic transformation process. Here we engineered lymphoma-prone mice with chromosomal instability to assess the usefulness of mouse models in cancer gene discovery and the extent of cross-species overlap in cancer-associated copy number aberrations. Along with targeted re-sequencing, our comparative oncogenomic studies identified FBXW7 and PTEN to be commonly deleted both in murine lymphomas and in human T-cell acute lymphoblastic leukaemia/lymphoma (T-ALL). The murine cancers acquire widespread recurrent amplifications and deletions targeting loci syntenic to those not only in human T-ALL but also in diverse human haematopoietic, mesenchymal and epithelial tumours. These results indicate that murine and human tumours experience common biological processes driven by orthologous genetic events in their malignant evolution. The highly concordant nature of genomic events encourages the use of genomically unstable murine cancer models in the discovery of biological driver events in the human oncogenome.
authors.affiliation: Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Maser
authors.forename: Bhudipa
authors.initials: B
authors.lastname: Choudhury
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Campbell
authors.forename: Bin
authors.initials: B
authors.lastname: Feng
authors.forename: Kwok-Kin
authors.initials: KK
authors.lastname: Wong
authors.forename: Alexei
authors.initials: A
authors.lastname: Protopopov
authors.forename: Jennifer
authors.initials: J
authors.lastname: O'Neil
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gutierrez
authors.forename: Elena
authors.initials: E
authors.lastname: Ivanova
authors.forename: Ilana
authors.initials: I
authors.lastname: Perna
authors.forename: Eric
authors.initials: E
authors.lastname: Lin
authors.forename: Vidya
authors.initials: V
authors.lastname: Mani
authors.forename: Shan
authors.initials: S
authors.lastname: Jiang
authors.forename: Kate
authors.initials: K
authors.lastname: McNamara
authors.forename: Sara
authors.initials: S
authors.lastname: Zaghlul
authors.forename: Sarah
authors.initials: S
authors.lastname: Edkins
authors.forename: Claire
authors.initials: C
authors.lastname: Stevens
authors.forename: Cameron
authors.initials: C
authors.lastname: Brennan
authors.forename: Eric S
authors.initials: ES
authors.lastname: Martin
authors.forename: Ruprecht
authors.initials: R
authors.lastname: Wiedemeyer
authors.forename: Omar
authors.initials: O
authors.lastname: Kabbarah
authors.forename: Cristina
authors.initials: C
authors.lastname: Nogueira
authors.forename: Gavin
authors.initials: G
authors.lastname: Histen
authors.forename: Jon
authors.initials: J
authors.lastname: Aster
authors.forename: Marc
authors.initials: M
authors.lastname: Mansour
authors.forename: Veronique
authors.initials: V
authors.lastname: Duke
authors.forename: Letizia
authors.initials: L
authors.lastname: Foroni
authors.forename: Adele K
authors.initials: AK
authors.lastname: Fielding
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Goldstone
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
authors.forename: Yaoqi A
authors.initials: YA
authors.lastname: Wang
authors.forename: A Thomas
authors.initials: AT
authors.lastname: Look
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stratton
authors.forename: Lynda
authors.initials: L
authors.lastname: Chin
authors.forename: P Andrew
authors.initials: PA
authors.lastname: Futreal
authors.forename: Ronald A
authors.initials: RA
authors.lastname: DePinho
mesh_terms: D000818:Animals; D043171:Chromosomal Instability / Q000235:genetics*; D002869:Chromosome Aberrations; D017124:Conserved Sequence / Q000235:genetics*; D016678:Genome / Q000235:genetics; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000235:genetics*; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics; D026801:Synteny / Q000235:genetics
chemical_list: D051059:PTEN Phosphohydrolase