title: A specific mode of microsatellite instability is a crucial biomarker in adult T-cell leukaemia/lymphoma patients.
abstract: OBJECTIVE
  Microsatellite instability (MSI) has been a long-standing biomarker candidate for drug resistance in tumour cells. Despite numerous clinical studies, the data in the literature are not conclusive. The complexity of the MSI phenomenon in some malignancies may, at least partly, account for the discrepancy. In addition, methodological problems are also pointed out in the assay techniques. We previously established a unique fluorescent technique in which the major methodological problems in conventional assays are overcome. Application of this technique has revealed two distinct modes of microsatellite alterations, i.e. Type A and Type B. More importantly, we demonstrated that Type A MSI is the direct consequence of defective DNA mismatch repair (MMR) that causes cellular resistance against antineoplastic agents.
  
  
  METHODS
  We first applied this technique to adult T-cell leukaemia/lymphoma (ATLL).
  
  
  RESULTS
  The MSI phenomenon was indeed observed in ATLLs (4/20, 20%). Intriguingly, the observed microsatellite alterations were invariably Type A, which implies that the tumours were MMR-defective. Indeed, clinical outcomes of patients with these MSI+tumours were significantly worse. Furthermore, multivariate analysis revealed that Type A MSI is an independent prognostic factor.
  
  
  CONCLUSIONS
  These observations strongly suggest the possibility of Type A MSI as a prognostic and potentially predictive biomarker in ATLL.
authors: Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, 811-1395, Japan.|Department of Hematology, National Kyushu Cancer Center, Fukuoka, 811-1395, Japan.|Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
authors: Kaname
authors: K
authors: Miyashita
authors: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
authors: Kei
authors: K
authors: Fujii
authors: Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, 811-1395, Japan.
authors: Kenichi
authors: K
authors: Taguchi
authors: Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, 811-1395, Japan.
authors: Mototsugu
authors: M
authors: Shimokawa
authors: Department of Radiation Biology, Institute of Radiation Emergency Medicine, Hirosaki University, Aomori, 036-8560, Japan.
authors: Mitsuaki A
authors: MA
authors: Yoshida
authors: Department of Hematology, National Kyushu Cancer Center, Fukuoka, 811-1395, Japan.
authors: Yasunobu
authors: Y
authors: Abe
authors: Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, 811-1395, Japan.
authors: Jun
authors: J
authors: Okamura
authors: Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, 811-1395, Japan. soda@nk-cc.go.jp.
authors: Shinya
authors: S
authors: Oda
authors: Department of Hematology, National Kyushu Cancer Center, Fukuoka, 811-1395, Japan.
authors: Naokuni
authors: N
authors: Uike
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D053208:Kaplan-Meier Estimate; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1 / Q000096:biosynthesis / Q000235:genetics*; D051718:MutS Homolog 2 Protein / Q000096:biosynthesis / Q000235:genetics*; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C501486:MLH1 protein, human; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein
keywords: Adult T-cell leukaemia/lymphoma; Biomarker; Chemotherapy; DNA mismatch repair; Drug resistance; Microsatellite instability