A Ser49Cys Variant in the Ataxia Telangiectasia, Mutated, Gene that Is More Common in Patients with Breast Carcinoma Compared with Population Controls

Thomas A. Buchholz, Michael M. Weil, Cheryl L. Ashorn, Eric A. Strom, Alice Sigurdson, Melissa Bondy, Ranajit Chakraborty, James D. Cox, Marsha D. McNeese, Michael D. Story

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

BACKGROUND. Mothers of children who have ataxia telangiectasia have been reported to be at increased risk for development of breast carcinoma. To test whether sequence variants in the ataxia telangiectasia, mutated, gene (ATM) are associated with breast carcinoma, the authors compared the frequency of ATM cDNA sequence changes in patients with breast carcinoma with the corresponding frequency in control patients. METHODS. The authors sequenced ATM cDNA from 91 patients with breast carcinoma and compared the frequencies of sequence changes in these patients with the corresponding frequencies in a control sample of 940 individuals with no history of malignant disease. RESULTS. Thirty-five patients with breast carcinoma had one or more single-base changes in ATM. Three genetic variants were found in at least two patients. These variants resulted in Asp1853Asn, Pro1054Arg, or Ser49Cys amino acid substitutions in the ATM protein. The Ser49Cys variant was more common in patients with breast carcinoma than in the control patients, with respective frequencies of 6.7% (5 of 75 patients) and 1.3% (12 of 940 patients; P = 0.006; Fisher two-sided exact test). The subgroup of patients with bilateral breast carcinoma had a Ser49Cys frequency of 11.8% (2 of 17 patients), which again was significantly different from what was observed in the control group (P = 0.024; Fisher two-sided exact test). The allele frequencies of the other two variants were not different between case patients and control patients. CONCLUSIONS. Patients with breast carcinoma, particularly those with bilateral disease, were more likely to have a variant in the ATM gene that resulted in a Ser49Cys substitution in the gene product. Additional studies are needed to evaluate the potential functional consequences of the Ser49Cys substitution and confirm the relevance of this variant in the development of breast carcinoma.

Original languageEnglish (US)
Pages (from-to)1345-1351
Number of pages7
JournalCancer
Volume100
Issue number7
DOIs
StatePublished - Apr 1 2004

Fingerprint

Population Control
Breast Neoplasms
Genes
Ataxia Telangiectasia
Ataxia-Telangiectasia Variant
Complementary DNA
Ataxia Telangiectasia Mutated Proteins
Amino Acid Substitution
Gene Frequency

Keywords

  • Ataxia telangiectasia
  • Breast carcinoma
  • Gene
  • Mutated
  • Polymorphisms
  • Variants

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A Ser49Cys Variant in the Ataxia Telangiectasia, Mutated, Gene that Is More Common in Patients with Breast Carcinoma Compared with Population Controls. / Buchholz, Thomas A.; Weil, Michael M.; Ashorn, Cheryl L.; Strom, Eric A.; Sigurdson, Alice; Bondy, Melissa; Chakraborty, Ranajit; Cox, James D.; McNeese, Marsha D.; Story, Michael D.

In: Cancer, Vol. 100, No. 7, 01.04.2004, p. 1345-1351.

Research output: Contribution to journalArticle

Buchholz, TA, Weil, MM, Ashorn, CL, Strom, EA, Sigurdson, A, Bondy, M, Chakraborty, R, Cox, JD, McNeese, MD & Story, MD 2004, 'A Ser49Cys Variant in the Ataxia Telangiectasia, Mutated, Gene that Is More Common in Patients with Breast Carcinoma Compared with Population Controls', Cancer, vol. 100, no. 7, pp. 1345-1351. https://doi.org/10.1002/cncr.20133
Buchholz, Thomas A. ; Weil, Michael M. ; Ashorn, Cheryl L. ; Strom, Eric A. ; Sigurdson, Alice ; Bondy, Melissa ; Chakraborty, Ranajit ; Cox, James D. ; McNeese, Marsha D. ; Story, Michael D. / A Ser49Cys Variant in the Ataxia Telangiectasia, Mutated, Gene that Is More Common in Patients with Breast Carcinoma Compared with Population Controls. In: Cancer. 2004 ; Vol. 100, No. 7. pp. 1345-1351.
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abstract = "BACKGROUND. Mothers of children who have ataxia telangiectasia have been reported to be at increased risk for development of breast carcinoma. To test whether sequence variants in the ataxia telangiectasia, mutated, gene (ATM) are associated with breast carcinoma, the authors compared the frequency of ATM cDNA sequence changes in patients with breast carcinoma with the corresponding frequency in control patients. METHODS. The authors sequenced ATM cDNA from 91 patients with breast carcinoma and compared the frequencies of sequence changes in these patients with the corresponding frequencies in a control sample of 940 individuals with no history of malignant disease. RESULTS. Thirty-five patients with breast carcinoma had one or more single-base changes in ATM. Three genetic variants were found in at least two patients. These variants resulted in Asp1853Asn, Pro1054Arg, or Ser49Cys amino acid substitutions in the ATM protein. The Ser49Cys variant was more common in patients with breast carcinoma than in the control patients, with respective frequencies of 6.7{\%} (5 of 75 patients) and 1.3{\%} (12 of 940 patients; P = 0.006; Fisher two-sided exact test). The subgroup of patients with bilateral breast carcinoma had a Ser49Cys frequency of 11.8{\%} (2 of 17 patients), which again was significantly different from what was observed in the control group (P = 0.024; Fisher two-sided exact test). The allele frequencies of the other two variants were not different between case patients and control patients. CONCLUSIONS. Patients with breast carcinoma, particularly those with bilateral disease, were more likely to have a variant in the ATM gene that resulted in a Ser49Cys substitution in the gene product. Additional studies are needed to evaluate the potential functional consequences of the Ser49Cys substitution and confirm the relevance of this variant in the development of breast carcinoma.",
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T1 - A Ser49Cys Variant in the Ataxia Telangiectasia, Mutated, Gene that Is More Common in Patients with Breast Carcinoma Compared with Population Controls

AU - Buchholz, Thomas A.

AU - Weil, Michael M.

AU - Ashorn, Cheryl L.

AU - Strom, Eric A.

AU - Sigurdson, Alice

AU - Bondy, Melissa

AU - Chakraborty, Ranajit

AU - Cox, James D.

AU - McNeese, Marsha D.

AU - Story, Michael D.

PY - 2004/4/1

Y1 - 2004/4/1

N2 - BACKGROUND. Mothers of children who have ataxia telangiectasia have been reported to be at increased risk for development of breast carcinoma. To test whether sequence variants in the ataxia telangiectasia, mutated, gene (ATM) are associated with breast carcinoma, the authors compared the frequency of ATM cDNA sequence changes in patients with breast carcinoma with the corresponding frequency in control patients. METHODS. The authors sequenced ATM cDNA from 91 patients with breast carcinoma and compared the frequencies of sequence changes in these patients with the corresponding frequencies in a control sample of 940 individuals with no history of malignant disease. RESULTS. Thirty-five patients with breast carcinoma had one or more single-base changes in ATM. Three genetic variants were found in at least two patients. These variants resulted in Asp1853Asn, Pro1054Arg, or Ser49Cys amino acid substitutions in the ATM protein. The Ser49Cys variant was more common in patients with breast carcinoma than in the control patients, with respective frequencies of 6.7% (5 of 75 patients) and 1.3% (12 of 940 patients; P = 0.006; Fisher two-sided exact test). The subgroup of patients with bilateral breast carcinoma had a Ser49Cys frequency of 11.8% (2 of 17 patients), which again was significantly different from what was observed in the control group (P = 0.024; Fisher two-sided exact test). The allele frequencies of the other two variants were not different between case patients and control patients. CONCLUSIONS. Patients with breast carcinoma, particularly those with bilateral disease, were more likely to have a variant in the ATM gene that resulted in a Ser49Cys substitution in the gene product. Additional studies are needed to evaluate the potential functional consequences of the Ser49Cys substitution and confirm the relevance of this variant in the development of breast carcinoma.

AB - BACKGROUND. Mothers of children who have ataxia telangiectasia have been reported to be at increased risk for development of breast carcinoma. To test whether sequence variants in the ataxia telangiectasia, mutated, gene (ATM) are associated with breast carcinoma, the authors compared the frequency of ATM cDNA sequence changes in patients with breast carcinoma with the corresponding frequency in control patients. METHODS. The authors sequenced ATM cDNA from 91 patients with breast carcinoma and compared the frequencies of sequence changes in these patients with the corresponding frequencies in a control sample of 940 individuals with no history of malignant disease. RESULTS. Thirty-five patients with breast carcinoma had one or more single-base changes in ATM. Three genetic variants were found in at least two patients. These variants resulted in Asp1853Asn, Pro1054Arg, or Ser49Cys amino acid substitutions in the ATM protein. The Ser49Cys variant was more common in patients with breast carcinoma than in the control patients, with respective frequencies of 6.7% (5 of 75 patients) and 1.3% (12 of 940 patients; P = 0.006; Fisher two-sided exact test). The subgroup of patients with bilateral breast carcinoma had a Ser49Cys frequency of 11.8% (2 of 17 patients), which again was significantly different from what was observed in the control group (P = 0.024; Fisher two-sided exact test). The allele frequencies of the other two variants were not different between case patients and control patients. CONCLUSIONS. Patients with breast carcinoma, particularly those with bilateral disease, were more likely to have a variant in the ATM gene that resulted in a Ser49Cys substitution in the gene product. Additional studies are needed to evaluate the potential functional consequences of the Ser49Cys substitution and confirm the relevance of this variant in the development of breast carcinoma.

KW - Ataxia telangiectasia

KW - Breast carcinoma

KW - Gene

KW - Mutated

KW - Polymorphisms

KW - Variants

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