Frequency of EGFR and KRAS mutations in lung adenocarcinomas in African Americans.
BACKGROUND
The detection of mutations in the epidermal growth factor receptor (EGFR) gene, which predict sensitivity to treatment with EGFR tyrosine kinase inhibitors, represents a major advance in the treatment of lung adenocarcinoma. KRAS mutations confer resistance to EGFR-tyrosine kinase inhibitors. The prevalence of these mutations in African American patients has not been thoroughly investigated.


METHODS
We collected formalin-fixed, paraffin-embedded material from resected lung adenocarcinomas from African American patients at three institutions for DNA extraction. The frequencies of EGFR exon 19 deletions, exon 21 L858R substitutions, and KRAS mutations in tumor specimens from African American patients were compared with data in white patients (n = 476).


RESULTS
EGFR mutations were detected in 23 of the 121 specimens from African American patients (19%, 95% confidence interval [CI]: 13-27%), whereas KRAS mutations were found in 21 (17%, 95% CI: 12-25%). There was no significant difference between frequencies of EGFR mutations comparing African American and white patients, 19% versus 13% (61/476, 95% CI: 10-16%; p = 0.11). KRAS mutations were more likely among whites, 26% (125/476, 95% CI: 23-30%; p = 0.04).


CONCLUSIONS
This is the largest study to date examining the frequency of mutations in lung adenocarcinomas in African Americans. Although KRAS mutations were somewhat less likely, there was no difference between the frequencies of EGFR mutations in African American patients, when compared with whites. These results suggest that all patients with advanced lung adenocarcinomas should undergo mutational analysis before initiation of therapy.
Memorial Sloan-Kettering Cancer Center, New York City, New York 10065, USA.
J Matthew
JM
Reinersman
Melissa L
ML
Johnson
Gregory J
GJ
Riely
Dhananjay A
DA
Chitale
Anthony D
AD
Nicastri
Gerald A
GA
Soff
Ann G
AG
Schwartz
Camelia S
CS
Sima
Getinet
G
Ayalew
Christopher
C
Lau
Maureen F
MF
Zakowski
Valerie W
VW
Rusch
Marc
M
Ladanyi
Mark G
MG
Kris
D000230:Adenocarcinoma / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D001741:Black or African American / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D044465:White People / Q000235:genetics; D018631:ras Proteins / Q000235:genetics*
D004273:DNA, Neoplasm; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins