PMID- 28609363
OWN - NLM
STAT- MEDLINE
DCOM- 20180410
LR  - 20180803
IS  - 1536-4828 (Electronic)
IS  - 0885-3177 (Linking)
VI  - 46
IP  - 6
DP  - 2017 Jul
TI  - O6-Methylguanine DNA Methyltransferase Status Does Not Predict Response or
      Resistance to Alkylating Agents in Well-Differentiated Pancreatic Neuroendocrine 
      Tumors.
PG  - 758-763
LID - 10.1097/MPA.0000000000000842 [doi]
AB  - OBJECTIVES: Alkylating agents have activity in well-differentiated pancreatic
      neuroendocrine tumors (WD panNETs). In glioblastoma multiforme, decreased
      activity of O-methylguanine DNA methyltransferase (MGMT) predicts response; in
      panNETs, MGMT relevance is unknown. METHODS: We identified patients with WD
      panNETs treated with alkylating agents, determined best overall response by
      Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, and performed MGMT
      activity testing. RESULTS: Fifty-six patients were identified; 26 (46%) of the 56
      patients experienced partial response, 24 (43%) of 56 experienced stable disease,
      and 6 (11%) of 56 experienced progression of disease. O-methylguanine DNA
      methyltransferase status was available for 36 tumors. For tumors with partial
      response, 10 (67%) of 15 were MGMT deficient, and 5 (33%) of 15 were MGMT intact.
      For tumors with stable disease, 7 (47%) of 15 were MGMT deficient, and 8 (53%) of
      15 were MGMT intact. For tumors with progression of disease, 3 (50%) of 6 were
      MGMT deficient, and 3 (50%) of 6 were MGMT intact. CONCLUSIONS: We observed
      response and resistance to alkylating agents in MGMT-deficient and MGMT-intact
      tumors. O-methylguanine DNA methyltransferase status should not guide alkylating 
      agent therapy in WD panNETs.
FAU - Raj, Nitya
AU  - Raj N
AD  - From the Departments of *Medicine, daggerPathology, double daggerRadiology,
      section signBiostatistics, and parallelSurgery, Memorial Sloan Kettering Cancer
      Center, New York, NY.
FAU - Klimstra, David S
AU  - Klimstra DS
FAU - Horvat, Natally
AU  - Horvat N
FAU - Zhang, Liying
AU  - Zhang L
FAU - Chou, Joanne F
AU  - Chou JF
FAU - Capanu, Marinela
AU  - Capanu M
FAU - Basturk, Olca
AU  - Basturk O
FAU - Do, Richard Kinh Gian
AU  - Do RKG
FAU - Allen, Peter J
AU  - Allen PJ
FAU - Reidy-Lagunes, Diane
AU  - Reidy-Lagunes D
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Pancreas
JT  - Pancreas
JID - 8608542
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 7GR28W0FJI (Dacarbazine)
RN  - EC 2.1.1.- (DNA Modification Methylases)
RN  - EC 2.1.1.63 (MGMT protein, human)
RN  - EC 6.5.1.- (DNA Repair Enzymes)
RN  - YF1K15M17Y (temozolomide)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents, Alkylating/adverse effects/*therapeutic use
MH  - Biomarkers, Tumor/*analysis/genetics
MH  - *Cell Differentiation
MH  - Child
MH  - DNA Methylation
MH  - DNA Modification Methylases/*analysis/genetics
MH  - DNA Repair Enzymes/*analysis/genetics
MH  - Dacarbazine/adverse effects/*analogs & derivatives/*therapeutic use
MH  - Databases, Factual
MH  - Disease Progression
MH  - *Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Grading
MH  - Neuroendocrine Tumors/*drug therapy/enzymology/genetics/pathology
MH  - Pancreatic Neoplasms/*drug therapy/enzymology/genetics/pathology
MH  - Pharmacogenetics
MH  - Promoter Regions, Genetic
MH  - Sequence Analysis, DNA
MH  - Time Factors
MH  - Treatment Outcome
MH  - Tumor Suppressor Proteins/*analysis/genetics
MH  - Young Adult
PMC - PMC5509357
MID - NIHMS870034
EDAT- 2017/06/14 06:00
MHDA- 2018/04/11 06:00
CRDT- 2017/06/14 06:00
PHST- 2017/06/14 06:00 [entrez]
PHST- 2017/06/14 06:00 [pubmed]
PHST- 2018/04/11 06:00 [medline]
AID - 10.1097/MPA.0000000000000842 [doi]
AID - 00006676-201707000-00008 [pii]
PST - ppublish
SO  - Pancreas. 2017 Jul;46(6):758-763. doi: 10.1097/MPA.0000000000000842.