Impact of variant reclassification in cancer predisposition genes on clinical care
PURPOSE: Genetic testing has clinical utility in the management of patients with hereditary cancer syndromes. However, the increased likelihood of encountering a variant of uncertain significance in individuals of non- European descent such as Asians may be challenging to both clinicians and patient...
Saved in:
Main Authors: | , , , , , , , , , |
---|---|
Other Authors: | |
Format: | Article |
Language: | English |
Published: |
2023
|
Subjects: | |
Online Access: | https://hdl.handle.net/10356/170423 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Nanyang Technological University |
Language: | English |
id |
sg-ntu-dr.10356-170423 |
---|---|
record_format |
dspace |
spelling |
sg-ntu-dr.10356-1704232023-09-12T01:58:59Z Impact of variant reclassification in cancer predisposition genes on clinical care Chiang, Jianbang Chia, Tze Hao Yuen, Jeanette Shaw, Tarryn Li, Shao-Tzu Nur Diana Binte Ishak Chew, Ee Ling Chong, Siao Ting Chan, Sock Hoai Ngeow, Joanne Lee Kong Chian School of Medicine (LKCMedicine) National Cancer Centre Singapore Duke-NUS Medical School Institute of Molecular and Cellular Biology, A*STAR Science::Medicine Cancer Genetics Retrospective Study PURPOSE: Genetic testing has clinical utility in the management of patients with hereditary cancer syndromes. However, the increased likelihood of encountering a variant of uncertain significance in individuals of non- European descent such as Asians may be challenging to both clinicians and patients. This study aims to evaluate the impact of variant reclassification in an Asian country with variants of uncertain significance reported in cancer predisposition genes. METHODS: A retrospective analysis of patients seen at the Cancer Genetics Service at the National Cancer Centre Singapore between February 2014 and March 2020 was conducted. The frequency, direction, and time to variant reclassification were evaluated by comparing the reclassified report against the original report. RESULTS: A total of 1,412 variants of uncertain significance were reported in 49.9% (845 of 1,695) of patients. Over 6 years, 6.7% (94 of 1,412) of variants were reclassified. Most variants of uncertain significance (94.1%, 80 of 85) were downgraded to benign or likely benign variant, with a smaller proportion of variants of uncertain significance (5.9%, 5 of 85) upgraded to pathogenic or likely pathogenic variant. Actionable variants of uncertain significance upgrades and pathogenic or likely pathogenic variant downgrades, which resulted in management changes, happened in 31.0% (39 of 126) of patients. The median and mean time taken for reclassification were 1 and 1.62 year(s), respectively. CONCLUSION: We propose a clinical guideline to standardize management of patients reported to have variants of uncertain significance. Management should be based on the patient's personal history, family history, and variant interpretation. For clinically relevant or suspicious variants of uncertain significance, follow-up is recommended every 2 years, as actionable reclassifications may happen during this period. Ministry of Health (MOH) National Medical Research Council (NMRC) National Research Foundation (NRF) Supported by the National Research Foundation Singapore under its Clinical Scientist Award (NMRC/CSA-INV/0017/2017) and administered by the Singapore Ministry of Health’s National Medical Research Council. This project was partially funded by NCC Research Fund, NCC Cancer Fund, and Terry Fox supporting funds. J.N. was funded by the National Medical Research Council Singapore and also received research funding from AstraZeneca. 2023-09-12T01:58:58Z 2023-09-12T01:58:58Z 2021 Journal Article Chiang, J., Chia, T. H., Yuen, J., Shaw, T., Li, S., Nur Diana Binte Ishak, Chew, E. L., Chong, S. T., Chan, S. H. & Ngeow, J. (2021). Impact of variant reclassification in cancer predisposition genes on clinical care. JCO Precision Oncology, 5(5), 577-584. https://dx.doi.org/10.1200/PO.20.00399 2473-4284 https://hdl.handle.net/10356/170423 10.1200/PO.20.00399 34994607 2-s2.0-85120181921 5 5 577 584 en NMRC/CSA-INV/0017/2017 JCO Precision Oncology © 2023 American Society of Clinical Oncology. All rights reserved. |
institution |
Nanyang Technological University |
building |
NTU Library |
continent |
Asia |
country |
Singapore Singapore |
content_provider |
NTU Library |
collection |
DR-NTU |
language |
English |
topic |
Science::Medicine Cancer Genetics Retrospective Study |
spellingShingle |
Science::Medicine Cancer Genetics Retrospective Study Chiang, Jianbang Chia, Tze Hao Yuen, Jeanette Shaw, Tarryn Li, Shao-Tzu Nur Diana Binte Ishak Chew, Ee Ling Chong, Siao Ting Chan, Sock Hoai Ngeow, Joanne Impact of variant reclassification in cancer predisposition genes on clinical care |
description |
PURPOSE: Genetic testing has clinical utility in the management of patients with hereditary cancer syndromes. However, the increased likelihood of encountering a variant of uncertain significance in individuals of non- European descent such as Asians may be challenging to both clinicians and patients. This study aims to evaluate the impact of variant reclassification in an Asian country with variants of uncertain significance reported in cancer predisposition genes. METHODS: A retrospective analysis of patients seen at the Cancer Genetics Service at the National Cancer Centre Singapore between February 2014 and March 2020 was conducted. The frequency, direction, and time to variant reclassification were evaluated by comparing the reclassified report against the original report. RESULTS: A total of 1,412 variants of uncertain significance were reported in 49.9% (845 of 1,695) of patients. Over 6 years, 6.7% (94 of 1,412) of variants were reclassified. Most variants of uncertain significance (94.1%, 80 of 85) were downgraded to benign or likely benign variant, with a smaller proportion of variants of uncertain significance (5.9%, 5 of 85) upgraded to pathogenic or likely pathogenic variant. Actionable variants of uncertain significance upgrades and pathogenic or likely pathogenic variant downgrades, which resulted in management changes, happened in 31.0% (39 of 126) of patients. The median and mean time taken for reclassification were 1 and 1.62 year(s), respectively. CONCLUSION: We propose a clinical guideline to standardize management of patients reported to have variants of uncertain significance. Management should be based on the patient's personal history, family history, and variant interpretation. For clinically relevant or suspicious variants of uncertain significance, follow-up is recommended every 2 years, as actionable reclassifications may happen during this period. |
author2 |
Lee Kong Chian School of Medicine (LKCMedicine) |
author_facet |
Lee Kong Chian School of Medicine (LKCMedicine) Chiang, Jianbang Chia, Tze Hao Yuen, Jeanette Shaw, Tarryn Li, Shao-Tzu Nur Diana Binte Ishak Chew, Ee Ling Chong, Siao Ting Chan, Sock Hoai Ngeow, Joanne |
format |
Article |
author |
Chiang, Jianbang Chia, Tze Hao Yuen, Jeanette Shaw, Tarryn Li, Shao-Tzu Nur Diana Binte Ishak Chew, Ee Ling Chong, Siao Ting Chan, Sock Hoai Ngeow, Joanne |
author_sort |
Chiang, Jianbang |
title |
Impact of variant reclassification in cancer predisposition genes on clinical care |
title_short |
Impact of variant reclassification in cancer predisposition genes on clinical care |
title_full |
Impact of variant reclassification in cancer predisposition genes on clinical care |
title_fullStr |
Impact of variant reclassification in cancer predisposition genes on clinical care |
title_full_unstemmed |
Impact of variant reclassification in cancer predisposition genes on clinical care |
title_sort |
impact of variant reclassification in cancer predisposition genes on clinical care |
publishDate |
2023 |
url |
https://hdl.handle.net/10356/170423 |
_version_ |
1779156360681750528 |