Genetic abnormalities of the EGFR pathway in African American patients with non-small-cell lung cancer

Rom S. Leidner, Pingfu Fu, Bradley Clifford, Ayad Hamdan, Cheng Jin, Rosana Eisenberg, Titus J. Boggon, Margaret SkokanM., Wilbur A. Franklin, Federico Cappuzzo, Fred R. Hirsch, Marileila Varella-Garcia, Balazs Halmos

Research output: Contribution to journalArticle

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Abstract

Purpose: Previous studies in non-small-cell lung cancer (NSCLC) have demonstrated a wide variation in responsiveness to epidermal growth factor receptor (EGFR) -targeting agents and in genetic aberrancies of the EGFR pathway according to ethnic background, most notably a higher frequency of activating EGFR mutations among East-Asian patients. We investigated the frequency of EGFR pathway aberrancies among African American patients with NSCLC, for whom limited information presently exists. Patients and Methods: EGFR fluorescent in situ hybridization (FISH) was performed on archived tissues from 53 African American patients. Extracted DNA was sequenced for mutational analysis of EGFR exons 18 to 21 and KRAS exon 2. Results were compared by multivariate analysis to an historical control cohort of 102 white patients with NSCLC. Results: African Americans were significantly less likely to harbor activating mutations of EGFR than white patients (2% v 17%; P = .022). Only one EGFR mutation was identified, a novel S768N substitution. EGFR FISH assay was more frequently positive for African Americans than for white patients (51% v 32%; P = .018). KRAS mutational frequency did not differ between the groups (23% v 21%; P = .409). Conclusion: African American patients with NSCLC are significantly less likely than white counterparts to harbor activating mutations of EGFR, which suggests that EGFR tyrosine kinase inhibitors (TKIs) are unlikely to yield major remissions in this population. Our findings add to a growing body of evidence that points to genetic heterogeneity of the EGFR pathway in NSCLC among different ethnic groups and that underscores the need for consideration of these differences in the design of future trials of agents that target the EGFR pathway.

Original languageEnglish (US)
Pages (from-to)5620-5626
Number of pages7
JournalJournal of Clinical Oncology
Volume27
Issue number33
DOIs
StatePublished - Nov 20 2009
Externally publishedYes

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Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
African Americans
Mutation
Fluorescence In Situ Hybridization
Exons
Genetic Heterogeneity
Ethnic Groups
Protein-Tyrosine Kinases
Multivariate Analysis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Genetic abnormalities of the EGFR pathway in African American patients with non-small-cell lung cancer. / Leidner, Rom S.; Fu, Pingfu; Clifford, Bradley; Hamdan, Ayad; Jin, Cheng; Eisenberg, Rosana; Boggon, Titus J.; SkokanM., Margaret; Franklin, Wilbur A.; Cappuzzo, Federico; Hirsch, Fred R.; Varella-Garcia, Marileila; Halmos, Balazs.

In: Journal of Clinical Oncology, Vol. 27, No. 33, 20.11.2009, p. 5620-5626.

Research output: Contribution to journalArticle

Leidner, RS, Fu, P, Clifford, B, Hamdan, A, Jin, C, Eisenberg, R, Boggon, TJ, SkokanM., M, Franklin, WA, Cappuzzo, F, Hirsch, FR, Varella-Garcia, M & Halmos, B 2009, 'Genetic abnormalities of the EGFR pathway in African American patients with non-small-cell lung cancer', Journal of Clinical Oncology, vol. 27, no. 33, pp. 5620-5626. https://doi.org/10.1200/JCO.2009.23.1431
Leidner, Rom S. ; Fu, Pingfu ; Clifford, Bradley ; Hamdan, Ayad ; Jin, Cheng ; Eisenberg, Rosana ; Boggon, Titus J. ; SkokanM., Margaret ; Franklin, Wilbur A. ; Cappuzzo, Federico ; Hirsch, Fred R. ; Varella-Garcia, Marileila ; Halmos, Balazs. / Genetic abnormalities of the EGFR pathway in African American patients with non-small-cell lung cancer. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 33. pp. 5620-5626.
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AU - Clifford, Bradley

AU - Hamdan, Ayad

AU - Jin, Cheng

AU - Eisenberg, Rosana

AU - Boggon, Titus J.

AU - SkokanM., Margaret

AU - Franklin, Wilbur A.

AU - Cappuzzo, Federico

AU - Hirsch, Fred R.

AU - Varella-Garcia, Marileila

AU - Halmos, Balazs

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N2 - Purpose: Previous studies in non-small-cell lung cancer (NSCLC) have demonstrated a wide variation in responsiveness to epidermal growth factor receptor (EGFR) -targeting agents and in genetic aberrancies of the EGFR pathway according to ethnic background, most notably a higher frequency of activating EGFR mutations among East-Asian patients. We investigated the frequency of EGFR pathway aberrancies among African American patients with NSCLC, for whom limited information presently exists. Patients and Methods: EGFR fluorescent in situ hybridization (FISH) was performed on archived tissues from 53 African American patients. Extracted DNA was sequenced for mutational analysis of EGFR exons 18 to 21 and KRAS exon 2. Results were compared by multivariate analysis to an historical control cohort of 102 white patients with NSCLC. Results: African Americans were significantly less likely to harbor activating mutations of EGFR than white patients (2% v 17%; P = .022). Only one EGFR mutation was identified, a novel S768N substitution. EGFR FISH assay was more frequently positive for African Americans than for white patients (51% v 32%; P = .018). KRAS mutational frequency did not differ between the groups (23% v 21%; P = .409). Conclusion: African American patients with NSCLC are significantly less likely than white counterparts to harbor activating mutations of EGFR, which suggests that EGFR tyrosine kinase inhibitors (TKIs) are unlikely to yield major remissions in this population. Our findings add to a growing body of evidence that points to genetic heterogeneity of the EGFR pathway in NSCLC among different ethnic groups and that underscores the need for consideration of these differences in the design of future trials of agents that target the EGFR pathway.

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