Subgroup-specific structural variation across 1,000 medulloblastoma genomes

• Authors: NORTHCOTT Paul A.; PEACOCK John; MORRISSY A Sorana; STUETZ Adrian M.; REIMAND Jueri; BEROUKHIM Rameen; MARSHALL Christian R.; MACK Stephen; YAO Yuan; LUU Betty; CAVALLI Florence M.G.; REMKE Marc; CHIU Readman Y. B.; CHUAH Eric; HOAD Gemma R.; LI Yisu; MUNGALL Karen L.; QIAN Jenny Q.; THIESSEN Nina; BIROL Inanc; MUNGALL Andrew J.; KAWAUCHI Daisuke; KOOL Marcel; WITT Hendrick; KENNEY Anna M.; DIRKS Peter; GRAJKOWSKA Wieslawa A.; HABERLER Christine C.; REYNAUD Stephanie S.; PERNET-FATTET Sarah S.; KIM Seung-Ki; SCHEURLEN Wolfram; FEVRE-MONTANGE Michelle; POLLACK Ian F.; MURASZKO Karin M.; DI ROCCO Concezio; MICHIELS Erna M.C.; FRENCH Pim J.; OLSON James M.; ZITTERBART Karel; KŘEN Leoš; LACH Boleslaw; BIGNER Darell D.; ALBRECHT Steffen; LINDSEY Janet C.; GUPTA Nalin; BOGNAR Laszlo; VAN METER Timothy E.; TOMINAGA Teiji; LEONARD Jeffrey R.; LIAU Linda M.; FOULADI Maryam; CINALLI Giuseppe; HAUSER Peter; IOLASCON Achille; CARLOTTI Carlos G.; RA Young Shin; ZOLLO Massimo; CHAN Jennifer A.; SORENSEN Poul H.B.; POMEROY Scott L.; BADER Gary D.; HAWKINS Cynthia E.; SCHERER Stephen W.; MALKIN David; JONES Steven J.M.; PFISTER Stefan M.; TAYLOR Michael D.; SHIH David J. H.; GARZIA Livia; ZICHNER T.; KORSHUNOV A.; SCHUMACHER S.E.; ELLISON David W.; LIONEL A.C.; DUBUC A.; RAMASWAMY V.; ROLIDER A.; WANG X.; WU X.; CHU A.; CORBETT R.D.; JACKMAN S.D.; LO A.; NIP K.M.; RAYMOND A.; VARHOL R.A.; MOORE R.A.; HOLT R.; ROUSSEL M.F.; JONES D.T.W.; FERNANDEZ-L A.; WECHSLER-REYA R.J.; AVIV T.; PEREK-POLNIK M.; DELATTRE O.; DOZ F.F.; CHO B.K.; WANG K.CH.; EBERHART Charles G.; JOUVET A.; FAN X.; GILLESPIE G.Y.; MASSIMI L.; KLOOSTERHOF N.K.; KROS J.M.; ELLENBOGEN R.G.; THOMPSON R.C.; COOPER M.K.; MCLENDON R.E.; FONTEBASSO A.; JABADO N.; BAILEY S.; WEISS W.A.; KLEKNER A.; KUMABE T.; ELBABAA S.K.; RUBIN J.B.; VAN MEIR E.G.; NAKAMURA H.; GARAMI M.; SAAD A.G.; JUNG S.; VIBHAKAR R.; ROBINSON S.; FARIA C.C.; LEVY M.L.; MEYERSON M.; CHO Y.J.; TABORI U.; BOUFFET E.; RUTKA J.T.; CLIFFORD S.C.; KORBEL J.O.; MARRA M.A.
• Year of publication: 2012
• Type: Article in Periodical
• Magazine / Source: Nature
• MU Faculty or unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.1038/nature11327
• Field: Oncology and hematology
• Keywords: HEDGEHOG PATHWAY INHIBITOR; COPY-NUMBER ALTERATION; PARKINSONS-DISEASE; ALPHA-SYNUCLEIN; HUMAN CANCERS; BETA FAMILY; SYNPHILIN-1; PROTEIN; MYC; CHILDHOOD

Attached files

• nature11327.pdf

• Description: Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4 alpha. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kappa B signalling in Group 4, suggest future avenues for rational, targeted therapy.