Absence of mutations in the ATM gene in breast cancer patients with severe responses to radiotherapy.

The effectiveness of cancer radiotherapy is compromised by the small proportion (approximately 5%) of patients who sustain severe normal tissue damage after standard radiotherapy treatments. Predictive tests are required to identify these highly radiosensitive cases. Patients with the rare, recessiv...

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Main Authors:	Appleby, J. M., Barber, J. B., Levine, E., Varley, J. M., Taylor, A. M., Stankovic, T., Heighway, J., Warren, C., Scott, D.
Format:	Online
Language:	English
Published:	Nature Publishing Group 1997
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2228198/

id	pubmed-2228198
recordtype	oai_dc
spelling	pubmed-22281982009-09-10 Absence of mutations in the ATM gene in breast cancer patients with severe responses to radiotherapy. Appleby, J. M. Barber, J. B. Levine, E. Varley, J. M. Taylor, A. M. Stankovic, T. Heighway, J. Warren, C. Scott, D. Research Article The effectiveness of cancer radiotherapy is compromised by the small proportion (approximately 5%) of patients who sustain severe normal tissue damage after standard radiotherapy treatments. Predictive tests are required to identify these highly radiosensitive cases. Patients with the rare, recessively inherited, cancer-prone syndrome ataxia-telangiectasia (A-T) sustain extremely severe normal tissue necrosis after radiotherapy and their cultured cells are also highly radiosensitive. Clinically normal carriers (heterozygotes) of the A-T gene have an increased risk of breast cancer, account for approximately 4% of all breast cancer cases and show a modest increase in cellular radiosensitivity in vitro. It has been suggested that a substantial proportion of highly radiosensitive (HR) breast cancer patients may be A-T heterozygotes, and that screening for mutations in the A-T gene could be used as a predictive test. We have tested this hypothesis in a group of cancer patients who showed adverse reactions to radiotherapy. Sixteen HR breast cancer patients showing mainly acute reactions (and seven HR patients with other cancers) were tested for ATM mutations using the restriction endonuclease fingerprinting assay. No mutations typical of those found in obligate A-T heterozygotes were detected. If the estimate that 4% of breast cancer cases are A-T gene carriers is correct, then ATM mutations do not confer clinical radiosensitivity. These early results suggest that screening for ATM mutations in cancer patients may not be of value in predicting adverse reactions. Nature Publishing Group 1997 /pmc/articles/PMC2228198/ /pubmed/9413938 Text en
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Appleby, J. M. Barber, J. B. Levine, E. Varley, J. M. Taylor, A. M. Stankovic, T. Heighway, J. Warren, C. Scott, D.
spellingShingle	Appleby, J. M. Barber, J. B. Levine, E. Varley, J. M. Taylor, A. M. Stankovic, T. Heighway, J. Warren, C. Scott, D. Absence of mutations in the ATM gene in breast cancer patients with severe responses to radiotherapy.
author_facet	Appleby, J. M. Barber, J. B. Levine, E. Varley, J. M. Taylor, A. M. Stankovic, T. Heighway, J. Warren, C. Scott, D.
author_sort	Appleby, J. M.
title	Absence of mutations in the ATM gene in breast cancer patients with severe responses to radiotherapy.
title_short	Absence of mutations in the ATM gene in breast cancer patients with severe responses to radiotherapy.
title_full	Absence of mutations in the ATM gene in breast cancer patients with severe responses to radiotherapy.
title_fullStr	Absence of mutations in the ATM gene in breast cancer patients with severe responses to radiotherapy.
title_full_unstemmed	Absence of mutations in the ATM gene in breast cancer patients with severe responses to radiotherapy.
title_sort	absence of mutations in the atm gene in breast cancer patients with severe responses to radiotherapy.
description	The effectiveness of cancer radiotherapy is compromised by the small proportion (approximately 5%) of patients who sustain severe normal tissue damage after standard radiotherapy treatments. Predictive tests are required to identify these highly radiosensitive cases. Patients with the rare, recessively inherited, cancer-prone syndrome ataxia-telangiectasia (A-T) sustain extremely severe normal tissue necrosis after radiotherapy and their cultured cells are also highly radiosensitive. Clinically normal carriers (heterozygotes) of the A-T gene have an increased risk of breast cancer, account for approximately 4% of all breast cancer cases and show a modest increase in cellular radiosensitivity in vitro. It has been suggested that a substantial proportion of highly radiosensitive (HR) breast cancer patients may be A-T heterozygotes, and that screening for mutations in the A-T gene could be used as a predictive test. We have tested this hypothesis in a group of cancer patients who showed adverse reactions to radiotherapy. Sixteen HR breast cancer patients showing mainly acute reactions (and seven HR patients with other cancers) were tested for ATM mutations using the restriction endonuclease fingerprinting assay. No mutations typical of those found in obligate A-T heterozygotes were detected. If the estimate that 4% of breast cancer cases are A-T gene carriers is correct, then ATM mutations do not confer clinical radiosensitivity. These early results suggest that screening for ATM mutations in cancer patients may not be of value in predicting adverse reactions.
publisher	Nature Publishing Group
publishDate	1997
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2228198/
_version_	1611437184875757568

Absence of mutations in the ATM gene in breast cancer patients with severe responses to radiotherapy.

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