TY - JOUR
T1 - Correlation between Genetic Abnormalities in Induced Pluripotent Stem Cell-Derivatives and Abnormal Tissue Formation in Tumorigenicity Tests
AU - Yamamoto, Takako
AU - Sato, Yoji
AU - Yasuda, Satoshi
AU - Shikamura, Masayuki
AU - Tamura, Takashi
AU - Takenaka, Chiemi
AU - Takasu, Naoko
AU - Nomura, Masaki
AU - Dohi, Hiromi
AU - Takahashi, Masayo
AU - Mandai, Michiko
AU - Kanemura, Yonehiro
AU - Nakamura, Masaya
AU - Okano, Hideyuki
AU - Kawamata, Shin
N1 - Funding Information:
This study was supported by research grants from the Japan Ministry of Health, Labour and Welfare (MHLW) and the Japan Agency for Medical Research and Development (AMED) [grant numbers 17bk0104004h0005, JP20bk0104017, JP21bm0204001, JP21bk0104099].
Publisher Copyright:
© 2022 The Author(s)..
PY - 2022/5
Y1 - 2022/5
N2 - Cell therapy using induced pluripotent stem cell (iPSC) derivatives may result in abnormal tissue generation because the cells undergo numerous cycles of mitosis before clinical application, potentially increasing the accumulation of genetic abnormalities. Therefore, genetic tests may predict abnormal tissue formation after transplantation. Here, we administered iPSC derivatives with or without single-nucleotide variants (SNVs) and deletions in cancer-related genes with various genomic copy number variant (CNV) profiles into immunodeficient mice and examined the relationships between mutations and abnormal tissue formation after transplantation. No positive correlations were found between the presence of SNVs/deletions and the formation of abnormal tissues; the overall predictivity was 29%. However, a copy number higher than 3 was correlated, with an overall predictivity of 86%. Furthermore, we found CNV hotspots at 14q32.33 and 17q12 loci. Thus, CNV analysis may predict abnormal tissue formation after transplantation of iPSC derivatives and reduce the number of tumorigenicity tests.
AB - Cell therapy using induced pluripotent stem cell (iPSC) derivatives may result in abnormal tissue generation because the cells undergo numerous cycles of mitosis before clinical application, potentially increasing the accumulation of genetic abnormalities. Therefore, genetic tests may predict abnormal tissue formation after transplantation. Here, we administered iPSC derivatives with or without single-nucleotide variants (SNVs) and deletions in cancer-related genes with various genomic copy number variant (CNV) profiles into immunodeficient mice and examined the relationships between mutations and abnormal tissue formation after transplantation. No positive correlations were found between the presence of SNVs/deletions and the formation of abnormal tissues; the overall predictivity was 29%. However, a copy number higher than 3 was correlated, with an overall predictivity of 86%. Furthermore, we found CNV hotspots at 14q32.33 and 17q12 loci. Thus, CNV analysis may predict abnormal tissue formation after transplantation of iPSC derivatives and reduce the number of tumorigenicity tests.
KW - Census database
KW - Shibata List
KW - copy number variants
KW - single-nucleotide variants
KW - tumorigenicity test
KW - variation of allele frequency
KW - whole-genome sequencing
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U2 - 10.1093/stcltm/szac014
DO - 10.1093/stcltm/szac014
M3 - Article
C2 - 35445254
AN - SCOPUS:85131216458
SN - 2157-6564
VL - 11
SP - 527
EP - 538
JO - Stem cells translational medicine
JF - Stem cells translational medicine
IS - 5
ER -
