PMID- 16631464
OWN - NLM
STAT- MEDLINE
DCOM- 20060525
LR  - 20060424
IS  - 0165-4608 (Print)
IS  - 0165-4608 (Linking)
VI  - 166
IP  - 2
DP  - 2006 Apr 15
TI  - Methylthioadenosine phosphorylase gene deletions are frequently detected by 
      fluorescence in situ hybridization in conventional chondrosarcomas.
PG  - 95-100
AB  - Chondrosarcomas are the second most common primary malignant tumor of bone. 
      Chemotherapy for conventional chondrosarcomas is generally ineffective. 
      Methylthioadenosine phosphorylase (MTAP) is a ubiquitous enzyme, essential in the 
      salvage pathway of adenine and in methionine synthesis. MTAP-deficient cells are 
      more susceptible than wild-type cells to pharmacologic inhibitors of de novo 
      purine synthesis. Homozygous deletions of MTAP have been reported in hematologic 
      and solid tumor malignancies. Based on these observations, we investigated the 
      frequency of MTAP deletions in conventional, grade II chondrosarcomas by 
      fluorescence in situ hybridization (FISH) analysis: 23 conventional, grade II 
      chondrosarcoma patient samples from the Cleveland Clinic Foundation were analyzed 
      for MTAP deletions. Nuclei were successfully extracted from 14 of 23 samples (61% 
      evaluable) for FISH analysis: 7 of 14 samples (50%) showed either homozygous or 
      hemizygous deletion of the MTAP gene, 6 of 14 (43%) failed to show deletion, and 
      1 of 14 (7%) was inconclusive. These findings suggest that approximately one-half 
      of conventional, grade II chondrosarcomas may be preferentially sensitive to 
      pharmacologic inhibitors of de novo purine synthesis. The present study led to 
      development by the Intergroup Coalition Against Sarcomas of a phase II trial of 
      pemetrexed, a multitargeted anti-folate, for advanced chondrosarcomas.
FAU - Chow, Warren A
AU  - Chow WA
AD  - Department of Medical Oncology and Therapeutics Research, City of Hope Medical 
      Center, 1500 E. Duarte Road, Duarte, CA 91010, USA. wchow@coh.org
FAU - Bedell, Victoria
AU  - Bedell V
FAU - Gaytan, Popsie
AU  - Gaytan P
FAU - Borden, Ernest
AU  - Borden E
FAU - Goldblum, John
AU  - Goldblum J
FAU - Hicks, David
AU  - Hicks D
FAU - Slovak, Marilyn L
AU  - Slovak ML
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Genet Cytogenet
JT  - Cancer genetics and cytogenetics
JID - 7909240
RN  - EC 2.4.2.1 (Purine-Nucleoside Phosphorylase)
RN  - EC 2.4.2.28 (5'-methylthioadenosine phosphorylase)
SB  - IM
MH  - Chondrosarcoma/*enzymology/*genetics
MH  - Chromosomes, Human, Pair 9/genetics
MH  - *Gene Deletion
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Interphase/genetics
MH  - Purine-Nucleoside Phosphorylase/*genetics
EDAT- 2006/04/25 09:00
MHDA- 2006/05/26 09:00
CRDT- 2006/04/25 09:00
PHST- 2005/07/22 00:00 [received]
PHST- 2005/09/30 00:00 [revised]
PHST- 2005/10/03 00:00 [accepted]
PHST- 2006/04/25 09:00 [pubmed]
PHST- 2006/05/26 09:00 [medline]
PHST- 2006/04/25 09:00 [entrez]
AID - S0165-4608(05)00623-0 [pii]
AID - 10.1016/j.cancergencyto.2005.10.009 [doi]
PST - ppublish
SO  - Cancer Genet Cytogenet. 2006 Apr 15;166(2):95-100. doi: 
      10.1016/j.cancergencyto.2005.10.009.