PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Ribi, S.* ; Baumhoer, D. ; Lee, K.* ; Edison* ; Teo, A.S.* ; Madan, B.* ; Zhang, K.* ; Kohlmann, W.K.* ; Yao, F.* ; Lee, W.H.* ; Hoi, Q.* ; Cai, S.W.* ; Woo, X.Y.* ; Tan, P.L.* ; Jundt, G.* ; Smida, J. ; Nathrath, M. ; Sung, W.K.* ; Schiffman, J.D.* ; Virshup, D.M.* ; Hillmer, A.M.*

TP53 intron 1 hotspot rearrangements are specific to sporadic osteosarcoma and can cause Li-Fraumeni syndrome.

Oncotarget 6, 7727-7740 (2015)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Somatic mutations of TP53 are among the most common in cancer and germline mutations of TP53 (usually missense) can cause Li-Fraumeni syndrome (LFS). Recently, recurrent genomic rearrangements in intron 1 of TP53 have been described in osteosarcoma (OS), a highly malignant neoplasm of bone belonging to the spectrum of LFS tumors. Using whole-genome sequencing of OS, we found features of TP53 intron 1 rearrangements suggesting a unique mechanism correlated with transcription. Screening of 288 OS and 1,090 tumors of other types revealed evidence for TP53 rearrangements in 46 (16%) OS, while none were detected in other tumor types, indicating this rearrangement to be highly specific to OS. We revisited a four-generation LFS family where no TP53 mutation had been identified and found a 445 kb inversion spanning from the TP53 intron 1 towards the centromere. The inversion segregated with tumors in the LFS family. Cancers in this family had loss of heterozygosity, retaining the rearranged allele and resulting in TP53 expression loss. In conclusion, intron 1 rearrangements cause p53-driven malignancies by both germline and somatic mechanisms and provide an important mechanism of TP53 inactivation in LFS, which might in part explain the diagnostic gap of formerly classified "TP53 wild-type" LFS.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
6.359
1.250
38
40
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Tp53 ; Li-fraumeni Syndrome ; Osteosarcoma ; Cancer Genomics ; Structural Variations; P53 Isoforms; Genomic Rearrangements; Structural Variations; Lynch Syndrome; Cancer; Gene; Cells; Transcript; Families; Delta-133p53
Sprache englisch
Veröffentlichungsjahr 2015
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 1949-2553
e-ISSN 1949-2553
Zeitschrift OncoTarget
Quellenangaben Band: 6, Heft: 10, Seiten: 7727-7740 Artikelnummer: , Supplement: ,
Verlag Impact Journals LLC
Begutachtungsstatus Peer reviewed
Institut(e) CCG Osteosarcoma (PATH-KOS)
Institute of Radiation Biology (ISB)
Institute of Pathology (PATH)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30202 - Environmental Health
Forschungsfeld(er) Enabling and Novel Technologies
Radiation Sciences
PSP-Element(e) G-520800-001
G-500200-001
G-500300-001
PubMed ID 25762628
DOI 10.18632/oncotarget.3115
WOS ID WOS:000354885300028
Scopus ID 84928388789
Erfassungsdatum 2015-04-05
[➜Korrektur melden]