Virtual Library
Start Your Search
M. Isaka
Author of
-
+
P2.15 - SCLC/Neuroendocrine Tumors (ID 716)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P2.15-008 - Genomic Analysis to Assess a Molecular Signature in Japanese Patients with Pulmonary High Grade Neuroendocrine Carcinoma (ID 8912)
09:30 - 09:30 | Author(s): M. Isaka
- Abstract
Background:
Pulmonary neuroendocrine carcinoma, including small cell lung cancer (SCLC), large cell neuroendocrine carcinoma (LCNEC), and carcinoid tumor, is a highly malignant cancer with poor prognosis. Because of its rarity, the molecular information available to investigate suitable therapeutic targets is insufficient, and little advancement has been made in the development of molecular-targeted therapies for these patients. This study aimed to determine a molecular signature of pulmonary neuroendocrine carcinoma by genomic analysis to explore therapeutic targets.
Method:
Surgically resected primary tumor specimens obtained between January 2014 and June 2016 from 15 patients with neuroendocrine carcinoma [SCLC, 8; LCNEC, 6; typical carcinoid (TC), 1; categorized based on WHO classification] were subjected to whole-exome sequencing (WES) and gene-expression profiling (GEP). Corresponding peripheral blood samples were collected as controls to identify tumor-specific genetic alterations in WES. Written informed consent was obtained from all patients. WES was performed on an Ion Proton system. An Agilent SurePrint G3 Human Gene Expression 8×60K v2 Microarray was used to detect tumor-specific gene expression. Oncogenic fusions were detected by targeted RNA sequencing. Copy number alterations were detected by integrating copy numbers resulting from WES and GEP. Promising oncogenic genetic alterations were selected using the OncodriveFML and Cancer Genome Interpreter.
Result:
Patient characteristics were: median age, 67 years; men, 67% (10/15); smokers, 93% (14/15); ratio of stage I/II/III/IV (%), 40/47/13/0. The median tumor mutational burden (TMB) in SCLC and LCNEC was 7.6 mutations (mt)/Mb (1.1–11.3) and 8.0 mt/Mb (3.5–12.6), respectively, which were significantly higher than that in lung adenocarcinoma (1.6 mt/Mb; p = 0.0025, p = 0.009), but not in lung squamous cell carcinoma (5.6 mt/Mb). One patient with TC showed low TMB (0.7 mt/Mb) and harbored a truncating mutation in MEN1, indicating a typical molecular signature of carcinoid tumor. The commonly altered genes (≥ 20%) were TP53 [60%, mut, 8; downregulation (down), 1], RB1 (53%, mut, 6; down, 2), CCNE1 [27%, amplification (amp), 4], APC (27%, mut, 3; down, 1), and BCL2 (20%, amp, 3). All genetic alterations detected in TP53, RB1, and APC were putative loss-of-functions. We observed no significant differences in frequency of alterations in the commonly altered genes between SCLC and LCNEC. One patient with LCNEC harbored EGFR-activating mutation, indicating possibility that this tumor was combined LCNEC with adenocarcinoma.
Conclusion:
This study revealed a molecular signature in Japanese patients with pulmonary neuroendocrine carcinoma, which could contribute to the development of novel molecular-targeted therapies.
