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 language | English |
|---|---|
| Pages (from-to) | 1183-1195 |
| Number of pages | 13 |
| Journal | Leukemia Research |
| Volume | 32 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 1 2008 |
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All Science Journal Classification (ASJC) codes
- Hematology
- Oncology
- Cancer Research
Cite this
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 journal › Article
}
TY - JOUR
T1 - Frequent microsatellite instability in non-Hodgkin lymphomas irresponsive to chemotherapy
AU - Miyashita, Kaname
AU - Fujii, Kei
AU - Yamada, Yu
AU - Hattori, Hiroyoshi
AU - Taguchi, Kenichi
AU - Yamanaka, Takeharu
AU - Yoshida, Mitsuaki A.
AU - Okamura, Jun
AU - Oda, Shinya
AU - Muta, Koichiro
AU - Nawata, Hajime
AU - Takayanagi, Ryoichi
AU - Uike, Naokuni
PY - 2008/8/1
Y1 - 2008/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=42749091253&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=42749091253&partnerID=8YFLogxK
U2 - 10.1016/j.leukres.2007.11.024
DO - 10.1016/j.leukres.2007.11.024
M3 - Article
C2 - 18177936
AN - SCOPUS:42749091253
VL - 32
SP - 1183
EP - 1195
JO - Leukemia Research
JF - Leukemia Research
SN - 0145-2126
IS - 8
ER -