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Licensed Unlicensed Requires Authentication Published by De Gruyter August 8, 2022

Detection of DNA copy number alterations by matrix-assisted laser desorption/ionization time-of-flight mass spectrometric analysis of single nucleotide polymorphisms

  • Shengnan Jin ORCID logo , Dan Huang ORCID logo , Weijiang Jin ORCID logo , Yourong Wang , Hengrong Shao , Lisha Gong , Zhenni Luo , Zhengquan Yang , Ju Luan , Deyao Xie EMAIL logo and Chunming Ding ORCID logo EMAIL logo



Copy number alterations (CNAs) are frequently found in malignant tissues. Different approaches have been used for CNA detection. However, it is not easy to detect a large panel of CNA targets in heterogenous tumors.


We have developed a CNAs detection approach through quantitatively analyzed allelic imbalance by allelotyping single nucleotide polymorphisms (SNPs) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Furthermore, the copy number changes were quantified by real-competitive PCR (rcPCR) to distinguish loss of heterozygosity (LOH) and genomic amplification. The approach was used to validate the CNA regions detected by next generation sequencing (NGS) in early-stage lung carcinoma.


CNAs were detected in heterogeneous DNA samples where tumor DNA is present at only 10% through the SNP based allelotyping. In addition, two different types of CNAs (loss of heterozygosity and chromosome amplification) were able to be distinguished quantitatively by rcPCR. Validation on a total of 41 SNPs from the selected CNA regions showed that copy number changes did occur, and the tissues from early-stage lung carcinoma were distinguished from normal.


CNA detection by MALDI-TOF MS can be used for validating potentially interesting genomic regions identified from next generation sequencing, and for detecting CNAs in tumor tissues consisting of a mixture of neoplastic and normal cells.

Corresponding authors: Chunming Ding, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, P.R. China; and Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, P.R. China, Phone: +86 577 86690891, Fax: +86 577 86699779, E-mail: ; and Deyao Xie, Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, P.R. China, Phone: +86 13506667375, Fax: +86 577 55578999 ext. 667375, E-mail:

Shengnan Jin, Dan Huang and Weijiang Jin contributed equally to this work.

Funding source: High-Level Innovation Team of Universities in Zhejiang Province

Award Identifier / Grant number: 604090352/610

Funding source: Key Discipline of Zhejiang Province in Medical Technology (Fist Class, Category A)

Award Identifier / Grant number: 437601607

Funding source: Zhejiang Provincial Natural Science Foundation of China

Award Identifier / Grant number: LY19H160027


The authors thank all patients for participating in the study and the doctors and nurses for clinical support.

  1. Research funding: This work was supported by Zhejiang Provincial Natural Science Foundation of China (DX: Grant No. LY19H160027), High-Level Innovation Team of Universities in Zhejiang Province (CD: Grant No. 604090352/610), and Key Discipline of Zhejiang Province in Medical Technology (Fist Class, Category A) (Grant No. 437601607).

  2. Author contributions: Chunming Ding, Shengnan Jin and Deyao Xie design of the project, and led the writing of the manuscript. Chunming Ding, Shengnan Jin, Dan Huang, Weijiang Jin, Yourong Wang participated in study design and data interpretation; Hengrong Shao, Lisha Gong, Zhenni Luo, Zhengquan Yang, Ju Luan analyzed the data; Deyao Xie provided clinical expertise. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: The authors declare no competing interests.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The study was approved by the Clinical Research Ethics of the First Affiliated Hospital of Wenzhou Medical University (2019-ky-50).


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Supplementary Material

The online version of this article offers supplementary material (

Received: 2022-05-26
Accepted: 2022-07-20
Published Online: 2022-08-08
Published in Print: 2022-09-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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