EGFR dinucleotide repeat polymorphism as a prognostic indicator in non-small cell lung cancer

Sarita Dubey, Patricia Stephenson, Donna E. Levy, Judith A. Miller, Steven M. Keller, Joan H. Schiller, David H. Johnson, Jill M. Kolesar

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: The epidermal growth factor receptor (EGFR) has been implicated in tumor growth and progression. Intron 1 of the EGFR gene contains a polymorphic simple sequence repeat (SSR) of 14 to 21 CA dinucleotides, the length of which correlates inversely with the level of EGFR transcription. The authors hypothesized that a shorter length of tumor SSR would be associated with poorer survival in patients with non-small cell lung cancer (NSCLC). METHODS: Patients enrolled in Eastern Cooperative Oncology Group E3590 (a randomized, prospective trial of adjuvant therapy following resection of stages II and IIIa NSCLC) were randomized to radiation or radiation plus chemotherapy. Genomic DNA extracted from resected tumors was amplified for EGFR intron 1 by polymerase chain reaction and sequenced in a 3730XL DNA analyzer. RESULTS: One hundred fifty-seven primary tumors were sequenced, 106 (68%) of which were heterozygous for intron 1. The most common genotypes were allele lengths of 17/19 dinucleotides (17.8%), 17/18 (11.4%), and 19/19 (11.4%). Allele status (homozygous versus heterozygous) did not correlate with race, gender, weight, performance status, histology, stage, or survival. Shorter allele length (≤18 versus >18 CA dinucleotide repeats) was associated with squamous cell histology (p = 0.03). Allele sum of greater than 35 was associated with improved overall survival (log-rank p = 0.03, hazard ratio = 0.66). CONCLUSION: This is the first study to characterize the EGFR intron 1 SSR polymorphism in NSCLC. Tumors were most commonly heterozygous for SSR length. Squamous histology was associated with a shorter SSR. Longer sequences are associated with improved survival.

Original languageEnglish (US)
Pages (from-to)406-412
Number of pages7
JournalJournal of Thoracic Oncology
Volume1
Issue number5
DOIs
StatePublished - Jun 2006

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Dinucleotide Repeats
Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Microsatellite Repeats
Introns
Alleles
Histology
Survival
Neoplasms
Radiation
erbB-1 Genes
DNA
Epithelial Cells
Genotype
Weights and Measures
Drug Therapy
Polymerase Chain Reaction
Growth

Keywords

  • Allele
  • Intron 1
  • Simple sequence repeat

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Medicine(all)

Cite this

Dubey, S., Stephenson, P., Levy, D. E., Miller, J. A., Keller, S. M., Schiller, J. H., ... Kolesar, J. M. (2006). EGFR dinucleotide repeat polymorphism as a prognostic indicator in non-small cell lung cancer. Journal of Thoracic Oncology, 1(5), 406-412. https://doi.org/10.1097/01243894-200606000-00005

EGFR dinucleotide repeat polymorphism as a prognostic indicator in non-small cell lung cancer. / Dubey, Sarita; Stephenson, Patricia; Levy, Donna E.; Miller, Judith A.; Keller, Steven M.; Schiller, Joan H.; Johnson, David H.; Kolesar, Jill M.

In: Journal of Thoracic Oncology, Vol. 1, No. 5, 06.2006, p. 406-412.

Research output: Contribution to journalArticle

Dubey, S, Stephenson, P, Levy, DE, Miller, JA, Keller, SM, Schiller, JH, Johnson, DH & Kolesar, JM 2006, 'EGFR dinucleotide repeat polymorphism as a prognostic indicator in non-small cell lung cancer', Journal of Thoracic Oncology, vol. 1, no. 5, pp. 406-412. https://doi.org/10.1097/01243894-200606000-00005
Dubey, Sarita ; Stephenson, Patricia ; Levy, Donna E. ; Miller, Judith A. ; Keller, Steven M. ; Schiller, Joan H. ; Johnson, David H. ; Kolesar, Jill M. / EGFR dinucleotide repeat polymorphism as a prognostic indicator in non-small cell lung cancer. In: Journal of Thoracic Oncology. 2006 ; Vol. 1, No. 5. pp. 406-412.
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abstract = "BACKGROUND: The epidermal growth factor receptor (EGFR) has been implicated in tumor growth and progression. Intron 1 of the EGFR gene contains a polymorphic simple sequence repeat (SSR) of 14 to 21 CA dinucleotides, the length of which correlates inversely with the level of EGFR transcription. The authors hypothesized that a shorter length of tumor SSR would be associated with poorer survival in patients with non-small cell lung cancer (NSCLC). METHODS: Patients enrolled in Eastern Cooperative Oncology Group E3590 (a randomized, prospective trial of adjuvant therapy following resection of stages II and IIIa NSCLC) were randomized to radiation or radiation plus chemotherapy. Genomic DNA extracted from resected tumors was amplified for EGFR intron 1 by polymerase chain reaction and sequenced in a 3730XL DNA analyzer. RESULTS: One hundred fifty-seven primary tumors were sequenced, 106 (68{\%}) of which were heterozygous for intron 1. The most common genotypes were allele lengths of 17/19 dinucleotides (17.8{\%}), 17/18 (11.4{\%}), and 19/19 (11.4{\%}). Allele status (homozygous versus heterozygous) did not correlate with race, gender, weight, performance status, histology, stage, or survival. Shorter allele length (≤18 versus >18 CA dinucleotide repeats) was associated with squamous cell histology (p = 0.03). Allele sum of greater than 35 was associated with improved overall survival (log-rank p = 0.03, hazard ratio = 0.66). CONCLUSION: This is the first study to characterize the EGFR intron 1 SSR polymorphism in NSCLC. Tumors were most commonly heterozygous for SSR length. Squamous histology was associated with a shorter SSR. Longer sequences are associated with improved survival.",
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AU - Schiller, Joan H.

AU - Johnson, David H.

AU - Kolesar, Jill M.

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N2 - BACKGROUND: The epidermal growth factor receptor (EGFR) has been implicated in tumor growth and progression. Intron 1 of the EGFR gene contains a polymorphic simple sequence repeat (SSR) of 14 to 21 CA dinucleotides, the length of which correlates inversely with the level of EGFR transcription. The authors hypothesized that a shorter length of tumor SSR would be associated with poorer survival in patients with non-small cell lung cancer (NSCLC). METHODS: Patients enrolled in Eastern Cooperative Oncology Group E3590 (a randomized, prospective trial of adjuvant therapy following resection of stages II and IIIa NSCLC) were randomized to radiation or radiation plus chemotherapy. Genomic DNA extracted from resected tumors was amplified for EGFR intron 1 by polymerase chain reaction and sequenced in a 3730XL DNA analyzer. RESULTS: One hundred fifty-seven primary tumors were sequenced, 106 (68%) of which were heterozygous for intron 1. The most common genotypes were allele lengths of 17/19 dinucleotides (17.8%), 17/18 (11.4%), and 19/19 (11.4%). Allele status (homozygous versus heterozygous) did not correlate with race, gender, weight, performance status, histology, stage, or survival. Shorter allele length (≤18 versus >18 CA dinucleotide repeats) was associated with squamous cell histology (p = 0.03). Allele sum of greater than 35 was associated with improved overall survival (log-rank p = 0.03, hazard ratio = 0.66). CONCLUSION: This is the first study to characterize the EGFR intron 1 SSR polymorphism in NSCLC. Tumors were most commonly heterozygous for SSR length. Squamous histology was associated with a shorter SSR. Longer sequences are associated with improved survival.

AB - BACKGROUND: The epidermal growth factor receptor (EGFR) has been implicated in tumor growth and progression. Intron 1 of the EGFR gene contains a polymorphic simple sequence repeat (SSR) of 14 to 21 CA dinucleotides, the length of which correlates inversely with the level of EGFR transcription. The authors hypothesized that a shorter length of tumor SSR would be associated with poorer survival in patients with non-small cell lung cancer (NSCLC). METHODS: Patients enrolled in Eastern Cooperative Oncology Group E3590 (a randomized, prospective trial of adjuvant therapy following resection of stages II and IIIa NSCLC) were randomized to radiation or radiation plus chemotherapy. Genomic DNA extracted from resected tumors was amplified for EGFR intron 1 by polymerase chain reaction and sequenced in a 3730XL DNA analyzer. RESULTS: One hundred fifty-seven primary tumors were sequenced, 106 (68%) of which were heterozygous for intron 1. The most common genotypes were allele lengths of 17/19 dinucleotides (17.8%), 17/18 (11.4%), and 19/19 (11.4%). Allele status (homozygous versus heterozygous) did not correlate with race, gender, weight, performance status, histology, stage, or survival. Shorter allele length (≤18 versus >18 CA dinucleotide repeats) was associated with squamous cell histology (p = 0.03). Allele sum of greater than 35 was associated with improved overall survival (log-rank p = 0.03, hazard ratio = 0.66). CONCLUSION: This is the first study to characterize the EGFR intron 1 SSR polymorphism in NSCLC. Tumors were most commonly heterozygous for SSR length. Squamous histology was associated with a shorter SSR. Longer sequences are associated with improved survival.

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