PMID- 16567768
OWN - NLM
STAT- MEDLINE
DCOM- 20060509
LR  - 20221109
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 24
IP  - 12
DP  - 2006 Apr 20
TI  - Genomics identifies medulloblastoma subgroups that are enriched for specific 
      genetic alterations.
PG  - 1924-31
AB  - PURPOSE: Traditional genetic approaches to identify gene mutations in cancer are 
      expensive and laborious. Nonetheless, if we are to avoid rejecting effective 
      molecular targeted therapies, we must test these drugs in patients whose tumors 
      harbor mutations in the drug target. We hypothesized that gene expression 
      profiling might be a more rapid and cost-effective method of identifying tumors 
      that contain specific genetic abnormalities. MATERIALS AND METHODS: Gene 
      expression profiles of 46 samples of medulloblastoma were generated using the 
      U133av2 Affymetrix oligonucleotide array and validated using real-time reverse 
      transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. 
      Genetic abnormalities were confirmed using fluorescence in situ hybridization 
      (FISH) and direct sequencing. RESULTS: Unsupervised analysis of gene expression 
      profiles partitioned medulloblastomas into five distinct subgroups (subgroups A 
      to E). Gene expression signatures that distinguished these subgroups predicted 
      the presence of key molecular alterations that we subsequently confirmed by gene 
      sequence analysis and FISH. Subgroup-specific abnormalities included mutations in 
      the Wingless (WNT) pathway and deletion of chromosome 6 (subgroup B) and 
      mutations in the Sonic Hedgehog (SHH) pathway (subgroup D). Real-time RT-PCR 
      analysis of gene expression profiles was then used to predict accurately the 
      presence of mutations in the WNT and SHH pathways in a separate group of 31 
      medulloblastomas. CONCLUSION: Genome-wide expression profiles can partition large 
      tumor cohorts into subgroups that are enriched for specific genetic alterations. 
      This approach may assist ultimately in the selection of patients for future 
      clinical trials of molecular targeted therapies.
FAU - Thompson, Margaret C
AU  - Thompson MC
AD  - St Jude Children's Research Hospital, Memphis, TN 38105, USA.
FAU - Fuller, Christine
AU  - Fuller C
FAU - Hogg, Twala L
AU  - Hogg TL
FAU - Dalton, James
AU  - Dalton J
FAU - Finkelstein, David
AU  - Finkelstein D
FAU - Lau, Ching C
AU  - Lau CC
FAU - Chintagumpala, Murali
AU  - Chintagumpala M
FAU - Adesina, Adekunle
AU  - Adesina A
FAU - Ashley, David M
AU  - Ashley DM
FAU - Kellie, Stewart J
AU  - Kellie SJ
FAU - Taylor, Michael D
AU  - Taylor MD
FAU - Curran, Tom
AU  - Curran T
FAU - Gajjar, Amar
AU  - Gajjar A
FAU - Gilbertson, Richard J
AU  - Gilbertson RJ
LA  - eng
GR  - CA 21765/CA/NCI NIH HHS/United States
GR  - CA096832/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060327
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antineoplastic Agents/therapeutic use
MH  - Cerebellar Neoplasms/drug therapy/*genetics/pathology
MH  - Child
MH  - Child, Preschool
MH  - Cost-Benefit Analysis
MH  - DNA Mutational Analysis
MH  - Female
MH  - *Gene Expression Profiling/economics
MH  - *Genomics
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Infant, Newborn
MH  - Male
MH  - Medulloblastoma/drug therapy/*genetics/pathology
MH  - Patient Selection
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2006/03/29 09:00
MHDA- 2006/05/10 09:00
CRDT- 2006/03/29 09:00
PHST- 2006/03/29 09:00 [pubmed]
PHST- 2006/05/10 09:00 [medline]
PHST- 2006/03/29 09:00 [entrez]
AID - JCO.2005.04.4974 [pii]
AID - 10.1200/JCO.2005.04.4974 [doi]
PST - ppublish
SO  - J Clin Oncol. 2006 Apr 20;24(12):1924-31. doi: 10.1200/JCO.2005.04.4974. Epub 
      2006 Mar 27.