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Journal of Cancer Research and Clinical Oncology

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Open Access 01-03-2017 | Original Article – Cancer Research

A specific mode of microsatellite instability is a crucial biomarker in adult T-cell leukaemia/lymphoma patients

Authors: Kaname Miyashita, Kei Fujii, Kenichi Taguchi, Mototsugu Shimokawa, Mitsuaki A. Yoshida, Yasunobu Abe, Jun Okamura, Shinya Oda, Naokuni Uike

Published in: Journal of Cancer Research and Clinical Oncology | Issue 3/2017

Abstract

Purpose

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.

Method

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.

Conclusion

These observations strongly suggest the possibility of Type A MSI as a prognostic and potentially predictive biomarker in ATLL.

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Title: A specific mode of microsatellite instability is a crucial biomarker in adult T-cell leukaemia/lymphoma patients
Authors: Kaname Miyashita
Kei Fujii
Kenichi Taguchi
Mototsugu Shimokawa
Mitsuaki A. Yoshida
Yasunobu Abe
Jun Okamura
Shinya Oda
Naokuni Uike
Publication date: 01-03-2017
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 3/2017
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-016-2294-1

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