KRAS Exon 3 and PTEN Exon 7 Mutations in Small-cell Lung Cancer

Lei Lei , Zhi-ming Jiang , Cheng-hui Li , Hong-yang Lu

Current Medical Science ›› 2019, Vol. 39 ›› Issue (3) : 379 -384.

PDF
Current Medical Science ›› 2019, Vol. 39 ›› Issue (3) : 379 -384. DOI: 10.1007/s11596-019-2046-y
Article

KRAS Exon 3 and PTEN Exon 7 Mutations in Small-cell Lung Cancer

Author information +
History +
PDF

Abstract

Small cell lung cancer (SCLC) is recognized as one of the most aggressive and fatal malignant tumors. No significant improvement has been made to prolong the survival of SCLC patients. This study aimed to examine the mutation status of K-Ras (KRAS) and phosphatase and tensin homolog (PTEN) in SCLC patients in order to identify potential therapeutic targets for SCLC. Nineteen primary SCLC tumor specimens were enrolled in the study. Direct sequencing was performed to detect the mutations of KRAS exon 3 and PTEN exon 7 in the specimens. Kaplan- Meier and Cox regression analysis was performed to determine the overall survival (OS) of these SCLC patients. KRAS exon 3 mutation was found in 4 (21%) SCLC patients, and PTEN exon 7 mutation in only 1 (5%) SCLC patient. Kaplan Meier analysis showed that clinical stage and brain metastasis were significantly associated with OS (both P<0.05), but neither KRAS exon 3 mutation nor PTEN exon 7 mutation was significantly associated with OS (P>0.05). Cox proportional hazards regression model indicated that extensive stage of disease was the only independent negative prognostic factor for OS in SCLC patients. In conclusion, KRAS exon 3 and PTEN exon 7 mutations had no significant impact on OS of SCLC patients. Further study is still necessary to validate the molecular profiles of SCLC.

Keywords

gene / Ras / small cell lung carcinoma / prognosis

Cite this article

Download citation ▾
Lei Lei, Zhi-ming Jiang, Cheng-hui Li, Hong-yang Lu. KRAS Exon 3 and PTEN Exon 7 Mutations in Small-cell Lung Cancer. Current Medical Science, 2019, 39(3): 379-384 DOI:10.1007/s11596-019-2046-y

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

ChenW, ZhengR, BaadePD, et al.. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132

[2]

JettJR, SchildSE, KeslerKA, et al.. Treatment of small cell lung cancer: Diagnosis and management of lung cancer: American College of Chest Physicians evidence-based clinical practice guidelines. Chest, 2013, 143(5Suppl): e400S-19S

[3]

KempfE, RousseauB, BesseB, et al.. KRAS oncogene in lung cancer: focus on molecularly driven clinical trials. Eur Respir Rev, 2016, 25(139): 71-76

[4]

KodazH, TaştekinE, ErdoğanB, et al.. KRAS mutation in small cell lung carcinoma and extrapulmonary small cell cancer. Balkan Med J, 2016, 33(4): 407-410

[5]

LiJ, YenC, LiawD, et al.. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science, 1997, 275(5308): 1943-1947

[6]

LiuW, ZhouY, ReskeSN, et al.. PTEN mutation: many birds with one stone in tumorigenesis. Anticancer research, 2008, 28(6A): 3613-3619

[7]

CairnsP, OkamiK, HalachmiS, et al.. Frequent inactivation of PTEN/MMAC1 in primary prostate cancer. Cancer Res, 1997, 57(22): 4997-5000

[8]

RisingerJI, HayesAK, BerchuckA, et al.. PTEN/MMAC1 mutations in endometrial cancers. Cancer Res, 1997, 57(21): 4736-4738

[9]

ForgacsE, BiesterveldEJ, SekidoY, et al.. Mutation analysis of the PTEN/MMAC1 gene in lung cancer. Oncogene, 1998, 17(12): 1557-1565

[10]

KohnoT, TakahashiM, MandaR, et al.. Inactivation of the PTEN/MMAC1/TEP1 gene in human lung cancers. Genes Chromosomes Cancer, 1998, 22(2): 152-156

[11]

YokomizoA, TindallDJ, DrabkinH, et al.. PTEN/MMAC1 mutations identified in small cell, but not in non-small cell lung cancers. Oncogene, 1998, 17(4): 475-479

[12]

MickeP, FaldumA, MetzT, et al.. Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer—what limits limited disease?. Lung Cancer, 2002, 37(3): 271-276

[13]

WangZ, JiangZ, LuH. Molecular genetic profiling of small cell lung carcinoma in a Chinese cohort. Transl Cancer Res, 2019, 8(1): 255-261

[14]

PleasanceED, StephensPJ, O’mearaS, et al.. A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature, 2010, 463(7278): 184-190

[15]

ArringtonAK, HeinrichEL, LeeW, et al.. Prognostic and predictive roles of KRAS mutation in colorectal cancer. Int J Mol Sci, 2012, 13(10): 12153-12168

[16]

BamfordS, DawsonE, ForbesS, et al.. The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website. Br J Cancer, 2004, 91(2): 355-358

[17]

SmitsAJ, KummerJA, HinrichsJW, et al.. EGFR and KRAS mutations in lung carcinomas in the Dutch population: increased EGFR mutation frequency in malignant pleural effusion of lung adenocarcinoma. Cell Oncol (Dordr), 2012, 35(3): 189-196

[18]

KodazH, HacibekirogluI, ErdoganB, et al.. Association between specific KRAS mutations and the clinicopathological characteristics of colorectal tumors. Mol Clin Oncol, 2015, 3(1): 179-184

[19]

MurtazaB, BibiA, RashidM, et al.. Spectrum of K ras mutations in Pakistani colorectal cancer patients. Braz J Med Biol Res, 2014, 47(1): 35-41

[20]

FeldmanR, AstsaturovI, MillisS, et al.. Molecular profiling in small cell lung cancer and lung neuroendocrine tumors. Int J Radiat Oncol Biol Phys, 2014, 90(5): S7-S7

[21]

AbdelraoufF, SharpA, MauryaM, et al.. Focused molecular analysis of small cell lung cancer: feasibility in routine clinical practice. BMC Res Notes, 2015, 8: 688

[22]

SchafferBE, ParkKS, YiuG, et al.. Loss of p130 accelerates tumor development in a mouse model for human small-cell lung carcinoma. Cancer Res, 2010, 70(10): 3877-3883

[23]

PeiferM, Fernández-CuestaL, SosML, et al.. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet, 2012, 44(10): 1104-1110

[24]

LeslieNR, BruntonVG. Cell biology. Where Is PTEN? Science, 2013, 341(6144): 355-356

[25]

McFaddenDG, PapagiannakopoulosT, Taylor-WeinerA, et al.. Genetic and clonal dissection of murine small cell lung carcinoma progression by genome sequencing. Cell, 2014, 156(6): 1298-12311

[26]

MalkoskiSP, CleaverTG, ThompsonJJ, et al.. Role of PTEN in basal cell derived lung carcinogenesis. Mol Carcinog, 2014, 53(10): 841-846

[27]

RossJ, WangK, ElkadiO, et al.. Next-generation sequencing reveals frequent consistent genomic alterations in small cell undifferentiated lung cancer. J Clin Pathol, 2014, 67(9): 772-776

[28]

GeorgeJ, LimJS, JangSJ, et al.. Comprehensive genomic profiles of small cell lung cancer. Nature, 2015, 524(7563): 47-53

[29]

EbbenJD, YouM. Brain metastasis in lung cancer: Building a molecular and systems-level understanding to improve outcomes. Int J Biochem Cell Biol, 2016, 78: 288-296

[30]

GoncalvesPH, PetersonSL, VigneauFD, et al.. Risk of brain metastases in patients with nonmetastatic lung cancer: Analysis of the Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) data. Cancer, 2016, 122(12): 1921-1927

[31]

NosakiK, SetoT. The Role of Radiotherapy in the Treatment of Small-Cell Lung Cancer. Curr Treat Options Oncol, 2015, 16(12): 56

AI Summary AI Mindmap
PDF

98

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/