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Therapeutic Priority of the PI3K/AKT/mTOR Pathway in Small Cell Lung Cancers as Revealed by a Comprehensive Genomic Analysis
| Content Provider | Semantic Scholar |
|---|---|
| Author | Umemura, Shigeki Mimaki, Sachiyo Makinoshima, Hideki Tada, Satoshi Ishii, Genichiro Ohmatsu, Hironobu Niho, Seiji Yoh, Kiyotaka Matsumoto, Shingo Takahashi, Alexandre Morise, Masahiro Nakamura, Yuka Ochiai, Atsushi Nagai, Kanji Iwakawa, Reika Kohno, Takashi Yokota, Jun Ohe, Yuichiro Esumi, Hiroyasu Tsuchihara, Katsuya Goto, Koichi |
| Copyright Year | 2014 |
| Abstract | INTRODUCTION The information regarding therapeutically relevant genomic alterations in small cell lung cancer (SCLC) is not well developed. We analyzed the SCLC genome using an integrative approach to stratify the targetable alterations. METHODS We performed whole exon sequencing (n = 51) and copy number analysis (n =47) on surgically resected tumors and matched normal tissue samples from treatment-naive Japanese SCLC patients. RESULTS The demographics of the 51 patients included in this study were as follows: median age, 67 years (range, 42-86 years); female, 9 (18%); history of smoking, 50 (98%); and pathological stage I/II/III/IV, 28/13/9/1, respectively. The average number of nonsynonymous mutations was 209 (range, 41-639; standard deviation, 130). We repeatedly confirmed the high prevalence of inactivating mutations in TP53 and RB1, and the amplification of MYC family members. In addition, genetic alterations in the PI3K/AKT/mTOR pathway were detected in 36% of the tumors: PIK3CA, 6%; PTEN, 4%; AKT2, 9%; AKT3, 4%; RICTOR, 9%; and mTOR, 4%. Furthermore, the individual changes in this pathway were mutually exclusive. Importantly, the SCLC cells harboring active PIK3CA mutations were potentially targetable with currently available PI3K inhibitors. CONCLUSIONS The PI3K/AKT/mTOR pathway is distinguishable in SCLC genomic alterations. Therefore, a sequencing-based comprehensive analysis could stratify SCLC patients by potential therapeutic targets. |
| Starting Page | 1324 |
| Ending Page | 1331 |
| Page Count | 8 |
| File Format | PDF HTM / HTML |
| PubMed reference number | 25122428 |
| Alternate Webpage(s) | https://doi.org/10.1097/JTO.0000000000000250 |
| DOI | 10.1097/jto.0000000000000250 |
| Journal | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer |
| Volume Number | 9 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 1-Phosphatidylinositol 3-Kinase AKT2 gene Biopolymer Sequencing Body tissue Copy Number Demography Exons FRAP1 protein, human MTOR gene MYC gene Mutation Neoplasms Non-Small Cell Lung Carcinoma Operative Surgical Procedures PIK3CA protein, human Patients Proto-Oncogene Proteins c-akt RICTOR gene Small cell carcinoma of lung Smoke |
| Content Type | Text |
| Resource Type | Article |
