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M.T. Lilo
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-050 - Detection of PIK3CA Mutations, including a Novel Mutation of V344G in Exon 4, in Metastatic NSCLC: A Retrospective Study of 139 FNA Cases (ID 957)
09:30 - 09:30 | Author(s): M.T. Lilo
- Abstract
Background:
Several molecular alterations of PIK3CA (phosphatidylinositol-4,5-biphosphate 3-kinases, catalytic subunit alpha) signaling pathways have been detected in primary non-small cell lung carcinoma (NSCLC). These include genomic amplifications of the regulatory subunit p85 and the catalytic subunit p110 alpha, as well as mutations of the helical binding domain on exon 9 and the catalytic subunit on exon 20. A mutation in the PIK3CA gene is a much rarer event than amplification in NSCLCs (approximately 2% in primary NSCLCs). The clinical significance of PIK3CA mutations in carcinoma is still not fully understood and is controversial. For example, some have suggested that PIK3CA mutations are associated with a favorable prognosis in breast cancer, while others have found PIK3CA mutations to be associated with a poor prognosis in primary lung cancers. Additionally, PIK3CA alterations have been associated with EGFR, KRAS and AKT mutations in primary NSCLC. In this study, we have collected FNA specimens of metastatic NSCLCs, investigated PIK3CA mutations, and correlated the findings with other molecular results.
Methods:
We identified 139 fine needle aspiration (FNA) cases of metastatic NSCLC with targeted next-generation sequencing (NGS) analyses of AKT, BRAF, EGFR, ERBB2, KRAS, NRAS, and PIK3CA genes, as well as testing for ALK gene rearrangements by fluorescence in situ hybridization (FISH) at the Johns Hopkins Medical Institute.
Results:
LN: Lymph node; PL: Pleural fluid; PR Peritoneal fluid. (-): not detected.Age Sex Location Diagnosis PIK3CA Mutation (exon #) EGFR Mutation BRAF Mutation KRAS Mutation 63 F LN ADC R88Q (1) (-) V600E (-) 69 M LN ADC V344G(4) E709A (-) (-) G719C 53 F PL ADC V344G(4) T790M (-) (-) E746_A750del 68 M LN NSCLC E542K(9) (-) (-) (-) 58 M PL ADC E542K (9) T790M (-) (-) L747_A750delinsP S768_V769delinsIL (S768I + V769L) 55 F Pelvic Bone SqCC E545K(9) (-) (-) (-) 74 F LN ADC P539R(9) (-) (-) G12C 60 M PR ADC H1047R(20) T790M (-) (-) L858R K860I
Conclusion:
PIK3CA mutation was detected in 5.8% of metastatic NSCLCs. The majority of the mutations were located on exon 9 or exon 20; however, a rare mutation in exon 1 was seen in one case. Further, a novel mutation, to our knowledge, for NSCLC was detected (V344G) in exon 4 in two cases. Among PIK3CA mutations, 50.0%, 12.5%, and 12% were associated with EGFR, BRAF, and KRAS mutations, respectively. In contrast to primary NSCLC, we did not find any metastatic cases to contain both PIK3CA and AKT mutations. The unique role of PIK3CA mutation in metastatic NSCLC and its clinical implications need to be further investigated.
