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Title: Clinical relevance of screening checklists for detecting cancer predisposition syndromes in Asian childhood tumours
Authors: Chan, Sock Hoai
Chew, Winston
Nur Diana Binte Ishak
Lim, Weng Khong
Li, Shao-Tzu
Tan, Sheng Hui
Teo, Jing Xian
Shaw, Tarryn
Chang, Kenneth
Chen, Yong
Iyer, Prasad
Tan, Enrica Ee Kar
Seng, Michaela Su-Fern
Chan, Mei Yoke
Tan, Ah Moy
Low, Sharon Yin Yee
Soh, Shui Yen
Loh, Amos Hong Pheng
Ngeow, Joanne
Keywords: Science::Medicine
Issue Date: 2018
Source: Chan, S. H., Chew, W., Nur Diana Binte Ishak, Lim, W. K., Li, S.-T., Tan, S. H., . . . Ngeow, J. (2018). Clinical relevance of screening checklists for detecting cancer predisposition syndromes in Asian childhood tumours. NPJ Genomic Medicine, 3, 30-. doi:10.1038/s41525-018-0070-7
Journal: NPJ genomic medicine
Abstract: Assessment of cancer predisposition syndromes (CPS) in childhood tumours is challenging to paediatric oncologists due to inconsistent recognizable clinical phenotypes and family histories, especially in cohorts with unknown prevalence of germline mutations. Screening checklists were developed to facilitate CPS detection in paediatric patients; however, their clinical value have yet been validated. Our study aims to assess the utility of clinical screening checklists validated by genetic sequencing in an Asian cohort of childhood tumours. We evaluated 102 patients under age 18 years recruited over a period of 31 months. Patient records were reviewed against two published checklists and germline mutations in 100 cancer-associated genes were profiled through a combination of whole-exome sequencing and multiplex ligation-dependent probe amplification on blood-derived genomic DNA. Pathogenic germline mutations were identified in ten (10%) patients across six known cancer predisposition genes: TP53, DICER1, NF1, FH, SDHD and VHL. Fifty-four (53%) patients screened positive on both checklists, including all ten pathogenic germline carriers. TP53 was most frequently mutated, affecting five children with adrenocortical carcinoma, sarcomas and diffuse astrocytoma. Disparity in prevalence of germline mutations across tumour types suggested variable genetic susceptibility and implied potential contribution of novel susceptibility genes. Only five (50%) children with pathogenic germline mutations had a family history of cancer. We conclude that CPS screening checklists are adequately sensitive to detect at-risk children and are relevant for clinical application. In addition, our study showed that 10% of Asian paediatric solid tumours have a heritable component, consistent with other populations.
ISSN: 2056-7944
DOI: 10.1038/s41525-018-0070-7
Rights: © 2018 The Author(s). (published in partnership with the Center of Excellence in Genomic Medicine Research). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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