title: Frequent microsatellite instability in non-Hodgkin lymphomas irresponsive to chemotherapy.
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.
authors.affiliation: Institute for Clinical Research, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Kaname
authors.initials: K
authors.lastname: Miyashita
authors.forename: Kei
authors.initials: K
authors.lastname: Fujii
authors.forename: Yu
authors.initials: Y
authors.lastname: Yamada
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Hattori
authors.forename: Kenichi
authors.initials: K
authors.lastname: Taguchi
authors.forename: Takeharu
authors.initials: T
authors.lastname: Yamanaka
authors.forename: Mitsuaki A
authors.initials: MA
authors.lastname: Yoshida
authors.forename: Jun
authors.initials: J
authors.lastname: Okamura
authors.forename: Shinya
authors.initials: S
authors.lastname: Oda
authors.forename: Koichiro
authors.initials: K
authors.lastname: Muta
authors.forename: Hajime
authors.initials: H
authors.lastname: Nawata
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
authors.forename: Naokuni
authors.initials: N
authors.lastname: Uike
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053843:DNA Mismatch Repair; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005453:Fluorescence; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000235:genetics
chemical_list: C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein