O6-Methylguanine DNA Methyltransferase Status Does Not Predict Response or Resistance to Alkylating Agents in Well-Differentiated Pancreatic Neuroendocrine Tumors.


Journal Article

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.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.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.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.

Full Text

Duke Authors

Cited Authors

  • Raj, N; Klimstra, DS; Horvat, N; Zhang, L; Chou, JF; Capanu, M; Basturk, O; Do, RKG; Allen, PJ; Reidy-Lagunes, D

Published Date

  • July 2017

Published In

Volume / Issue

  • 46 / 6

Start / End Page

  • 758 - 763

PubMed ID

  • 28609363

Pubmed Central ID

  • 28609363

Electronic International Standard Serial Number (EISSN)

  • 1536-4828

International Standard Serial Number (ISSN)

  • 0885-3177

Digital Object Identifier (DOI)

  • 10.1097/MPA.0000000000000842


  • eng