PMID- 19476837
OWN - NLM
STAT- MEDLINE
DCOM- 20090618
LR  - 20211020
IS  - 1879-1190 (Electronic)
IS  - 1072-7515 (Print)
IS  - 1072-7515 (Linking)
VI  - 208
IP  - 5
DP  - 2009 May
TI  - Genotyping and expression analysis of IDO2 in human pancreatic cancer: a novel, 
      active target.
PG  - 781-7; discussion 787-9
LID - 10.1016/j.jamcollsurg.2008.12.018 [doi]
AB  - BACKGROUND: The recently discovered indoleamine 2,3-dioxygenase-2 (IDO2) gene has 
      2 functional polymorphisms that abolish its enzymatic activity. We hypothesize 
      that expression of the IDO2 enzyme in primary pancreatic ductal adenocarcinomas 
      (PDA) can help cancer cells evade immune detection. STUDY DESIGN: Because the 
      IDO2 enzyme might be the preferential target of d-1-methyl-tryptophan, a clinical 
      lead inhibitor of IDO currently being evaluated in phase I trials, we sequenced 
      IDO2 in 36 pancreatic specimens and evaluated its expression. RESULTS: We found 
      that 58% (21 of 36) of cases were heterozygous for the R248W polymorphism; 28% 
      (10 of 36) were homozygous wild-type; and only 14% (5 of 36) were homozygous for 
      the functionally inactive polymorphism. As for the Y359STOP polymorphism, we 
      found that 27% (10 of 36) of cases were heterozygous, 62% (22 of 36) were 
      homozygous wild-type, and only 11% (4 of 36) were homozygous for this 
      functionally inactive allele. Ruling out the possibility of compound polymorphic 
      variants, we estimated 75% of our resected patient cohort had an active IDO2 
      enzyme, with a conservative estimate that 58% of the patients had at least 1 
      functional allele. IDO2 was expressed in PDA tissue from each genetically 
      polymorphic subgroup. We also detected IDO2 protein expression in the genetically 
      distinct pancreatic cancer cell lines after exposure with interferon-gamma. 
      CONCLUSIONS: This is the first study to report IDO2 expression in PDA and related 
      cancers indicating that IDO2 genetic polymorphisms do not negate 
      interferon-gamma-inducible protein expression. Taken together, our data strongly 
      suggest that the clinical lead compound d-1-methyl-tryptophan might be useful in 
      treatment of PDA.
FAU - Witkiewicz, Agnieszka K
AU  - Witkiewicz AK
AD  - Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107, 
      USA.
FAU - Costantino, Christina L
AU  - Costantino CL
FAU - Metz, Richard
AU  - Metz R
FAU - Muller, Alexander J
AU  - Muller AJ
FAU - Prendergast, George C
AU  - Prendergast GC
FAU - Yeo, Charles J
AU  - Yeo CJ
FAU - Brody, Jonathan R
AU  - Brody JR
LA  - eng
GR  - R01 CA109542/CA/NCI NIH HHS/United States
GR  - R01 CA109542-03/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - J Am Coll Surg
JT  - Journal of the American College of Surgeons
JID - 9431305
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Carcinoma, Pancreatic Ductal/*enzymology/immunology
MH  - Cell Line, Tumor
MH  - Genotype
MH  - Humans
MH  - Immunoblotting
MH  - Immunohistochemistry
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/*genetics/*metabolism
MH  - Interferon-gamma/pharmacology
MH  - Pancreatic Neoplasms/*enzymology/immunology
MH  - *Polymorphism, Genetic
MH  - Sequence Analysis, DNA
MH  - Up-Regulation/physiology
PMC - PMC3176891
MID - NIHMS314786
EDAT- 2009/05/30 09:00
MHDA- 2009/06/19 09:00
PMCR- 2011/09/20
CRDT- 2009/05/30 09:00
PHST- 2008/11/30 00:00 [received]
PHST- 2008/12/02 00:00 [accepted]
PHST- 2009/05/30 09:00 [entrez]
PHST- 2009/05/30 09:00 [pubmed]
PHST- 2009/06/19 09:00 [medline]
PHST- 2011/09/20 00:00 [pmc-release]
AID - S1072-7515(09)00050-7 [pii]
AID - 10.1016/j.jamcollsurg.2008.12.018 [doi]
PST - ppublish
SO  - J Am Coll Surg. 2009 May;208(5):781-7; discussion 787-9. doi: 
      10.1016/j.jamcollsurg.2008.12.018.