Mutations in EGFR, BRAF and RAS are rare in triple-negative and basal-like breast cancers from Caucasian women

Tilch, E., Seidens, T., Cocciardi, S., Reid, L. E., Byrne, D., Simpson, P. T., Vargas, A. C., Cummings, M. C., Fox, S. B., Lakhani, S. R. and Chenevix Trench, G. (2014) Mutations in EGFR, BRAF and RAS are rare in triple-negative and basal-like breast cancers from Caucasian women. Breast Cancer Research and Treatment, 143 2: 385-392. doi:10.1007/s10549-013-2798-1


Author Tilch, E.
Seidens, T.
Cocciardi, S.
Reid, L. E.
Byrne, D.
Simpson, P. T.
Vargas, A. C.
Cummings, M. C.
Fox, S. B.
Lakhani, S. R.
Chenevix Trench, G.
Title Mutations in EGFR, BRAF and RAS are rare in triple-negative and basal-like breast cancers from Caucasian women
Formatted title
Mutations in EGFR, BRAF and RAS are rare in triple-negative and basal-like breast cancers from Caucasian women
Journal name Breast Cancer Research and Treatment   Check publisher's open access policy
ISSN 0167-6806
1573-7217
Publication date 2014-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1007/s10549-013-2798-1
Open Access Status
Volume 143
Issue 2
Start page 385
End page 392
Total pages 8
Place of publication New York, NY, United States
Publisher Springer
Language eng
Subject 2730 Oncology
1306 Cancer Research
Abstract Basal-like and triple-negative breast cancers usually display a high level of genomic instability and often carry TP53 mutations. Mutations in EGFR have been reported in about 10 % triple-negative tumours from Chinese women, and there is some evidence that triple-negative and basal-like tumours might carry additional mutations against which targeted therapies are available. We, therefore, sought to determine the frequency of 238 targetable mutations in 19 oncogenes (including EGFR) in a panel of basal-like and triple-negative breast cancers from Caucasian women. We used the OncoCarta panel to screen for 238 mutations across 19 common oncogenes in 107 basal-like and triple-negative breast cancers from Caucasian women. Mutations were then verified using Sanger sequencing or primer extension by iPLEX. We identified and validated 10 mutations across five genes. Most of the mutations were observed in the PIK3CA gene (18/107, 16.8 %), while mutations in KRAS, NRAS, MET and AKT1 were present in only one tumour each (1/107, 0.9 %). Among the missense substitutions in PIK3CA the point mutation resulting in the amino acid change H1047R was the most frequent (8/18, 44 %). All mutations were mutually exclusive, apart from one basal-like breast tumour which harboured mutations in both MET (p.T992I) and PIK3CA (p.H1047R). We did not identify any mutations in the EGFR gene. In conclusion, we found that with the exception of mutations in PIK3CA, these actionable oncogenic mutations on the Oncocarta panel are rare in basal-like and triple-negative breast cancers from Caucasian women. Custom panels, designed to detect mutations identified by exome sequencing of basal-like and triple-negative breast cancers, are, therefore, needed to identify women who might be eligible for targeted treatment.
Keyword Basal breast cancer
Mutations
OncoCarta
Triple-negative breast cancer
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 7 December 2013.

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2014 Collection
School of Medicine Publications
 
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Created: Fri, 31 Jan 2014, 19:12:10 EST by Roheen Gill on behalf of UQ Centre for Clinical Research