Frequent microsatellite instability in non-Hodgkin lymphomas irresponsive to chemotherapy

Kaname Miyashita, Kei Fujii, Yu Yamada, Hiroyoshi Hattori, Kenichi Taguchi, Takeharu Yamanaka, Mitsuaki A. Yoshida, Jun Okamura, Shinya Oda, Koichiro Muta, Hajime Nawata, Ryoichi Takayanagi, Naokuni Uike

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Microsatellite instability (MSI) in haematopoietic malignancies has been controversial. Particularly in non-Hodgkin lymphoma, the data published to date lack unity. Using a unique fluorescent technique, we found MSI in eight (14%) tumours in a panel of 59 carefully selected non-Hodgkin lymphoma patients. Our fluorescent technique also reveals two qualitatively distinct modes of MSI, i.e. Type A and Type B. Based on our previous studies using DNA mismatch repair (MMR) gene-knock out animals, we have concluded that Type A MSI is a direct consequence of defective MMR. MSI observed in non-Hodgkin lymphomas was uniformly Type A, which implies that MMR deficiency occurs in this malignancy. Intriguingly, in non-Hodgkin lymphoma patients treated by CHOP/VEPA-based therapies, response to chemotherapy was significantly worse in those with microsatellite-unstable tumours (p = 0.027). As a consequence, the patient outcomes at 1 year after treatment were significantly less favourable in this population (p = 0.046), although the survival difference was not statistically confirmed in a longer term. These findings suggest that in some non-Hodgkin lymphomas MMR deficiency may lead to drug resistance in tumour cells and, consequently, to poor patient outcomes. In non-Hodgkin lymphoma, MSI may be a potential biomarker that predicts the tumour response against chemotherapy.

Original languageEnglish
Pages (from-to)1183-1195
Number of pages13
JournalLeukemia Research
Volume32
Issue number8
DOIs
Publication statusPublished - Aug 2008

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

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