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Dynamics of Minimal Residual Disease in Neuroblastoma Patients

Neuroblastoma is a common extracranial solid tumor of neural crest (NC) origin that accounts for up to 15% of all pediatric cancer deaths. The disease arises from a transient population of NC cells that undergo an epithelial-mesenchymal transition (EMT) and generate diverse cell-types and tissues. P...

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Autores principales: Uemura, Suguru, Ishida, Toshiaki, Thwin, Khin Kyae Mon, Yamamoto, Nobuyuki, Tamura, Akihiro, Kishimoto, Kenji, Hasegawa, Daiichiro, Kosaka, Yoshiyuki, Nino, Nanako, Lin, Kyaw San, Takafuji, Satoru, Mori, Takeshi, Iijima, Kazumoto, Nishimura, Noriyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558004/
https://www.ncbi.nlm.nih.gov/pubmed/31214500
http://dx.doi.org/10.3389/fonc.2019.00455
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author Uemura, Suguru
Ishida, Toshiaki
Thwin, Khin Kyae Mon
Yamamoto, Nobuyuki
Tamura, Akihiro
Kishimoto, Kenji
Hasegawa, Daiichiro
Kosaka, Yoshiyuki
Nino, Nanako
Lin, Kyaw San
Takafuji, Satoru
Mori, Takeshi
Iijima, Kazumoto
Nishimura, Noriyuki
author_facet Uemura, Suguru
Ishida, Toshiaki
Thwin, Khin Kyae Mon
Yamamoto, Nobuyuki
Tamura, Akihiro
Kishimoto, Kenji
Hasegawa, Daiichiro
Kosaka, Yoshiyuki
Nino, Nanako
Lin, Kyaw San
Takafuji, Satoru
Mori, Takeshi
Iijima, Kazumoto
Nishimura, Noriyuki
author_sort Uemura, Suguru
collection PubMed
description Neuroblastoma is a common extracranial solid tumor of neural crest (NC) origin that accounts for up to 15% of all pediatric cancer deaths. The disease arises from a transient population of NC cells that undergo an epithelial-mesenchymal transition (EMT) and generate diverse cell-types and tissues. Patients with neuroblastoma are characterized by their extreme heterogeneity ranging from spontaneous regression to malignant progression. More than half of newly diagnosed patients present highly metastatic tumors and are stratified into a high-risk group with dismal outcome. As many as 20% of high-risk patients have residual disease that is refractory or progressive during induction chemotherapy. Although a majority of high-risk patients achieve remission, larger part of those patients has minimal residual disease (MRD) that causes relapse even after additional consolidation therapy. MRD is composed of drug-resistant tumor cells and dynamically presented as cancer stem cells (CSCs) in residual tumors, circulating tumor cells (CTCs) in peripheral blood (PB), and disseminated tumor cells (DTCs) in bone marrow (BM) and other metastatic sites. EMT appears to be a key mechanism for cancer cells to acquire MRD phenotypes and malignant aggressiveness. Due to the restricted availability of residual tumors, PB and BM have been used to isolate and analyze CTCs and DTCs to evaluate MRD in cancer patients. In addition, recent technical advances make it possible to use circulating tumor DNA (ctDNA) shed from tumor cells into PB for MRD evaluation. Because MRD can be detected by tumor-specific antigens, genetic or epigenetic changes, and mRNAs, numerous assays using different methods and samples have been reported to detect MRD in cancer patients. In contrast to the tumor-specific gene-rearrangement-positive acute lymphoblastic leukemia (ALL) and the oncogenic fusion-gene-positive chronic myelogenous leukemia (CML) and several solid tumors, the clinical significance of MRD remains to be established in neuroblastoma. Given the extreme heterogeneity of neuroblastoma, dynamics of MRD in neuroblastoma patients will hold a key to the clinical validation. In this review, we summarize the biology and detection methods of cancer MRD in general and evaluate the available assays and clinical significance of neuroblastoma MRD to clarify its dynamics in neuroblastoma patients.
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spelling pubmed-65580042019-06-18 Dynamics of Minimal Residual Disease in Neuroblastoma Patients Uemura, Suguru Ishida, Toshiaki Thwin, Khin Kyae Mon Yamamoto, Nobuyuki Tamura, Akihiro Kishimoto, Kenji Hasegawa, Daiichiro Kosaka, Yoshiyuki Nino, Nanako Lin, Kyaw San Takafuji, Satoru Mori, Takeshi Iijima, Kazumoto Nishimura, Noriyuki Front Oncol Oncology Neuroblastoma is a common extracranial solid tumor of neural crest (NC) origin that accounts for up to 15% of all pediatric cancer deaths. The disease arises from a transient population of NC cells that undergo an epithelial-mesenchymal transition (EMT) and generate diverse cell-types and tissues. Patients with neuroblastoma are characterized by their extreme heterogeneity ranging from spontaneous regression to malignant progression. More than half of newly diagnosed patients present highly metastatic tumors and are stratified into a high-risk group with dismal outcome. As many as 20% of high-risk patients have residual disease that is refractory or progressive during induction chemotherapy. Although a majority of high-risk patients achieve remission, larger part of those patients has minimal residual disease (MRD) that causes relapse even after additional consolidation therapy. MRD is composed of drug-resistant tumor cells and dynamically presented as cancer stem cells (CSCs) in residual tumors, circulating tumor cells (CTCs) in peripheral blood (PB), and disseminated tumor cells (DTCs) in bone marrow (BM) and other metastatic sites. EMT appears to be a key mechanism for cancer cells to acquire MRD phenotypes and malignant aggressiveness. Due to the restricted availability of residual tumors, PB and BM have been used to isolate and analyze CTCs and DTCs to evaluate MRD in cancer patients. In addition, recent technical advances make it possible to use circulating tumor DNA (ctDNA) shed from tumor cells into PB for MRD evaluation. Because MRD can be detected by tumor-specific antigens, genetic or epigenetic changes, and mRNAs, numerous assays using different methods and samples have been reported to detect MRD in cancer patients. In contrast to the tumor-specific gene-rearrangement-positive acute lymphoblastic leukemia (ALL) and the oncogenic fusion-gene-positive chronic myelogenous leukemia (CML) and several solid tumors, the clinical significance of MRD remains to be established in neuroblastoma. Given the extreme heterogeneity of neuroblastoma, dynamics of MRD in neuroblastoma patients will hold a key to the clinical validation. In this review, we summarize the biology and detection methods of cancer MRD in general and evaluate the available assays and clinical significance of neuroblastoma MRD to clarify its dynamics in neuroblastoma patients. Frontiers Media S.A. 2019-06-04 /pmc/articles/PMC6558004/ /pubmed/31214500 http://dx.doi.org/10.3389/fonc.2019.00455 Text en Copyright © 2019 Uemura, Ishida, Thwin, Yamamoto, Tamura, Kishimoto, Hasegawa, Kosaka, Nino, Lin, Takafuji, Mori, Iijima and Nishimura. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Uemura, Suguru
Ishida, Toshiaki
Thwin, Khin Kyae Mon
Yamamoto, Nobuyuki
Tamura, Akihiro
Kishimoto, Kenji
Hasegawa, Daiichiro
Kosaka, Yoshiyuki
Nino, Nanako
Lin, Kyaw San
Takafuji, Satoru
Mori, Takeshi
Iijima, Kazumoto
Nishimura, Noriyuki
Dynamics of Minimal Residual Disease in Neuroblastoma Patients
title Dynamics of Minimal Residual Disease in Neuroblastoma Patients
title_full Dynamics of Minimal Residual Disease in Neuroblastoma Patients
title_fullStr Dynamics of Minimal Residual Disease in Neuroblastoma Patients
title_full_unstemmed Dynamics of Minimal Residual Disease in Neuroblastoma Patients
title_short Dynamics of Minimal Residual Disease in Neuroblastoma Patients
title_sort dynamics of minimal residual disease in neuroblastoma patients
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558004/
https://www.ncbi.nlm.nih.gov/pubmed/31214500
http://dx.doi.org/10.3389/fonc.2019.00455
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