1566P - Concurrent genetic alterations in lung cancer: A comprehensive genomic profiling in a Japanese cohort

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Lung and other Thoracic Tumours
Pathology/Molecular Biology
Translational Research
Presenter Tetsuhiko Taira
Citation Annals of Oncology (2014) 25 (suppl_4): iv542-iv545. 10.1093/annonc/mdu357
Authors T. Taira1, H. Kenmotsu1, M. Serizawa2, K. Wakuda3, H. Akamatsu4, T. Shukuya5, A. Ono6, H. Imai7, T. Naito3, H. Murakami3, M. Endo8, T. Nakajima9, Y. Ohde10, N. Yamamoto11, Y. Koh4, T. Takahashi3
  • 1Division Of Thoracic Oncology, Shizuoka Cancer Center, 411-8777 - Shizuoka/JP
  • 2Drug Discovery And Development Division, Shizuoka Cancer Center Research Institute, Shizuoka/JP
  • 3Division Of Thoracic Oncology, Shizuoka Cancer Center, 411-8777 - Sunto-gun/JP
  • 4The Third Department Of Internal Medicine, Wakayama Medical University, Wakayama/JP
  • 5Dept. Of Respiratory Medicine, Juntendo University, Tokyo/JP
  • 6Thoracic Oncology Dept., Shizuoka Cancer Center, 411-8777 - Shizuoka/JP
  • 7Department Of Medicine And Molecular Science, Gunma University Graduate School of Medicine, 371-8511 - Gunma/JP
  • 8Division Of Diagnostic Radiology, Shizuoka Cancer Center, 411-8777 - Sunto-gun/JP
  • 9Division Of Diagnostic Pathology, Shizuoka Cancer Center, 411-8777 - Shizuoka/JP
  • 10Division Of Thoracic Surgery, Shizuoka Cancer Center, 411-8777 - Shizuoka/JP
  • 11Third Department Of Internal Medicine, Wakayama Medical University, Wakayama/JP

Abstract

Aim

Recently,genomic profiling of lung cancer has been elucidated. However, the characteristics of concurrent genetic alterations remain unclear because of its low frequency. We conducted the Shizuoka Lung Cancer Mutation Study to analyze genetic alterations in patients with thoracic malignancies.

Methods

A tumor genotyping panel was designed to assess 23 hotspot sites of genetic alterations in 9 genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN and HER2), and gene copy number gain in 5 genes (EGFR, MET, PIK3CA, FGFR1 and FGFR2), and ALK, ROS1, and RET fusions using pyroseqencing plus capillay electrophoresis, quantitative polymerase chain reaction (PCR), and reverse transcription PCR, respectively.

Results

Out of 674 lung cancer patients enrolled in our study between July 2011 and March 2013, a total of 50 (7.4%) patients were identified as carrying multiple genetic alterations (44 double, 6 triple mutations). Patient characteristics were as follows: median age (range) 70 (37-93) years; female 32%; never-smorker 24%; histology adenocarcinoma/ squamous cell carcinoma/ small cell carcinoma/ other 70/ 22/ 6/ 2 %. Of the 44 double genetic alterations, 6 patients carried EGFR+PIK3CA mutations; 5 EGFR double mutations (3 exon19del+L858R, 1 exon19del+T790M, 1 L858R+T790M, and 1 G719X+L861Q); 4 EGFR+KRAS mutations; 4 EGFR mutations+EGFR copy number gain; and 1 EGFR+BRAF mutations. Two patients carried EGFR mutations (exon19del or L858R)+ T790M and 3 patients carried EGFR mutations (exon19del or L858R)+MET gene copy number gain in pre-EGFR-TKI treatment setting. Fourteen patients with concurret EGFR(exon19del or L858R)+other mutations received EGFR-TKI treatment. As compared with single EGFR(exon19del or L858R) mutations group of our cohort, patients with concurrent EGFR(exon19del or L858R)+other mutations tend to have shorter survival, however there was no statistically significant difference (MST, 35.3 versus 18.5 months, respectively; p=0.08).

Conclusions

Concurrent genetic alterations were detected in 7.4% of patients with lung cancer in Japanese cohorts. EGFR mutations were not mutually exclusive with KRAS and BRAF mutations. T790M and MET gene copy number gain were detected in the patients before EGFR-TKI treatment.

Disclosure

All authors have declared no conflicts of interest.