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S. Dong
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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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P3.04-036 - Rare Discrepancies in a Driving Gene Alteration within Histologically Heterogeneous Primary Lung Cancers (ID 2229)
09:30 - 09:30 | Author(s): S. Dong
- Abstract
Background:
Most lung adenocarcinomas consist of a mixture of histological subtypes among which driving gene mutations occurred with different frequencies. However, little is known about intratumoral heterogeneity within histologically heterogeneous primary lung cancers. Investigating key driver genes in respective morphological pattern is crucial to clinical practice and personalized treatment.
Methods:
Morphologically different tumor areas within the same surgically resected primary tumors were extracted from tissue sections and the gene status in each growth pattern was analyzed. Driving genes, epidermal growth factor receptor (EGFR), KRAS, and rearrangements in echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), were assessed by assays of different sensitivity.
Results:
Seventy-nine consecutive, surgically resected, adenocarcinomas or adeno-squamouse cell carcinomas harboring a driving gene mutation or rearrangement (EGFR, n = 65; KARS, n = 10; EML4-ALK, n = 4) were selected. For EGFR mutations in adenocarcinomas, ITH occurred in 13.3% (8/60) as determined by direct sequencing, but in only 1.7% (1/60) by ARMS(P= 0.016). A consistent intratumoral EGFR mutation status was found within 5 histologically heterogeneous adeno-squamous cell carcinomas, as shown with ARMS. ITH among KRAS mutations were detected in 20% (2/10) of regions examined by direct sequencing ,whereas a consistent status (10/10) was obtained with HRM. There were no discrepancies in EML4-ALK rearrangements according to FISH for four tumors.
Conclusion:
Rare ITHs deriving from EGFR/KRAS/EML4-ALK alterations within histologically heterogeneous primary lung adenocarcinomas were found with methods of high sensitivity. Discrepancies might be due to the abundance of cells harboring driving gene and detection assays.
