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Chimerism Assay Using Single Nucleotide Polymorphisms Adjacent and in Linkage-Disequilibrium Enables Sensitive Disease Relapse Monitoring after Hematopoietic Stem-Cell Transplantation

Authors
 JinJu Kim  ;  Woobin Yun  ;  Yu Jin Park  ;  Jieun Seo  ;  Richard Dong Wook Lee  ;  Saeam Shin  ;  Hyun-Ji Lee  ;  In Suk Kim  ;  Jong Rak Choi  ;  Seung-Tae Lee 
Citation
 CLINICAL CHEMISTRY, Vol.67(5) : 781-787, 2021-04 
Journal Title
CLINICAL CHEMISTRY
ISSN
 0009-9147 
Issue Date
2021-04
Keywords
SNP ; STR ; chimerism ; hematopoietic stem-cell transplantation ; next-generation sequencing ; transplantation monitoring
Abstract
Background: Short tandem repeat (STR)-based chimerism analysis has been widely used for chimerism monitoring after hematopoietic stem-cell transplantation (HSCT), but technical artifacts can be problematic. We designed a chimerism assay using single nucleotide polymorphisms (SNPs) adjacent and in linkage-disequilibrium (CASAL), which doubly checked for SNP pairs, and thus could reduce background errors and increase analytical sensitivity.

Methods: CASAL targeted 84 SNP pairs within 10 bp distance and in perfect linkage-disequilibrium. Using undiluted and serially diluted samples, baseline error rates, and linearity was calculated. Clinical performance of CASAL was evaluated in comparison with a conventional STR assay, using 191 posttransplant samples from 42 patients with HSCT.

Results: CASAL had ∼10 times lower baseline error rates compared to that of ordinary next-generation sequencing. Limit of detection and quantification of CASAL were estimated to be 0.09 and 0.39%, respectively, with a linear range of 0.1-100%. CASAL correlated well with STR assay (r2 = 0.99) and the higher sensitivity enabled detection of low-level recipient chimerism and earlier prediction of relapse.

Conclusions: CASAL is a simple, analytically sensitive and accurate assay that can be used in clinical samples after HSCT with a higher performance compared to that of traditional assays. It should also be useful in other forensic and archeological testing.
Full Text
https://academic.oup.com/clinchem/article/67/5/781/6134872
DOI
10.1093/clinchem/hvab010
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
Shin, Saeam(신새암) ORCID logo https://orcid.org/0000-0003-1501-3923
Lee, Seung-Tae(이승태) ORCID logo https://orcid.org/0000-0003-1047-1415
Choi, Jong Rak(최종락) ORCID logo https://orcid.org/0000-0002-0608-2989
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184301
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