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 journalArticle

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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 1 2008

Fingerprint

Microsatellite Instability
Non-Hodgkin's Lymphoma
Drug Therapy
DNA Mismatch Repair
Neoplasms
Gene Knockout Techniques
Hematologic Neoplasms
Tumor Biomarkers
Drug Resistance
Microsatellite Repeats
Survival
Therapeutics
Population

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Miyashita, K., Fujii, K., Yamada, Y., Hattori, H., Taguchi, K., Yamanaka, T., ... Uike, N. (2008). Frequent microsatellite instability in non-Hodgkin lymphomas irresponsive to chemotherapy. Leukemia Research, 32(8), 1183-1195. https://doi.org/10.1016/j.leukres.2007.11.024

Frequent microsatellite instability in non-Hodgkin lymphomas irresponsive to chemotherapy. / Miyashita, Kaname; Fujii, Kei; Yamada, Yu; Hattori, Hiroyoshi; Taguchi, Kenichi; Yamanaka, Takeharu; Yoshida, Mitsuaki A.; Okamura, Jun; Oda, Shinya; Muta, Koichiro; Nawata, Hajime; Takayanagi, Ryoichi; Uike, Naokuni.

In: Leukemia Research, Vol. 32, No. 8, 01.08.2008, p. 1183-1195.

Research output: Contribution to journalArticle

Miyashita, K, Fujii, K, Yamada, Y, Hattori, H, Taguchi, K, Yamanaka, T, Yoshida, MA, Okamura, J, Oda, S, Muta, K, Nawata, H, Takayanagi, R & Uike, N 2008, 'Frequent microsatellite instability in non-Hodgkin lymphomas irresponsive to chemotherapy', Leukemia Research, vol. 32, no. 8, pp. 1183-1195. https://doi.org/10.1016/j.leukres.2007.11.024
Miyashita, Kaname ; Fujii, Kei ; Yamada, Yu ; Hattori, Hiroyoshi ; Taguchi, Kenichi ; Yamanaka, Takeharu ; Yoshida, Mitsuaki A. ; Okamura, Jun ; Oda, Shinya ; Muta, Koichiro ; Nawata, Hajime ; Takayanagi, Ryoichi ; Uike, Naokuni. / Frequent microsatellite instability in non-Hodgkin lymphomas irresponsive to chemotherapy. In: Leukemia Research. 2008 ; Vol. 32, No. 8. pp. 1183-1195.
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