Advances in Clinical and Experimental Medicine
2016, vol. 25, nr 3, May-June, p. 397–402
Publication type: original article
PIK3CA Mutations in Resected Small Cell Lung Cancer
1 Zhejiang Key Laboratory of Diagnosis & Treatment Technology for Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China
2 Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China
3 Zhejiang Institute for Food and Drug Control, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China
4 Department of Pathology, Zhejiang Cancer Hospital, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China
Background. Despite advances in chemotherapy and radiotherapy in recent decades, the prognosis for small cell lung cancer (SCLC) patients is still poor. Targeted therapies in SCLC must be applied systemically to target not only the primary tumor but also metastases. The phosphatidylinositol 3-kinase (PI3K)/AKT pathways play a key regulatory function in the survival, proliferation, energy metabolism and cellular architecture advantages of malignant cells. The phosphatidylinositol 3-kinase catalytic α (PIK3CA) gene, which encodes the p110α catalytic subunit, plays a key role in the activation of AKT downstream signaling and mammary tumor progression. More than 75% of PIK3CA mutations are clustered in the helical (exon 9) and catalytic domains (exon 20). There have been very few studies reporting the PIK3CA mutations status of patients with SCLC who have undergone surgical treatment in mainland China.
Objectives. The aim of the study was to investigate the PIK3CA mutation in SCLC.
Material and Methods. Reverse transcription polymerase chain reaction (RT-PCR) and direct sequencing technology was used to detect the PIK3CA mutation in 14 cases of retrospectively collected SCLC patients who underwent surgical treatment at Zhejiang Cancer Hospital, Hangzhou, PRC, between 2002 and 2010.
Results. The research revealed no mutations in exons 9 and 20 of the PIK3CA gene. A nucleotide alteration of A1634C (E545A) of exon 9 turned out to be a pseudogene-positive, because the mutation disappeared when near-duplicate detection was employed.
Conclusion. The incidence of PIK3CA mutation is low in SCLC patients, and the pseudogene-positive alteration of A1634C is prone to occur in exon 9 of PIK3CA mutations in human cancers.
PIK3CA, gene mutation, SCLC
- Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Cancer J Clin 2010, 60, 277–300.
- Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, Spitznagel EL, Piccirillo J: Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: Analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 2006, 24, 4539–4544.
- Patel AM, Dunn WF, Trastek VF: Staging systems of lung cancer. Mayo Clin Proc 1993, 68, 475–482.
- Giroux DJ, Rami-Porta R, Chansky K, Crowley JJ, Groome PA, Postmus PE, Rusch V, Sculier JP, Shepherd FA, Sobin L, Goldstraw P: International Association for the Study of Lung Cancer International Staging Committee: The IASLC Lung Cancer Staging Project: Data Elements for the Prospective Project. J Thorac Oncol 2009, 4, 679–683.
- Lu HY, Wang XJ, Mao WM: Targeted therapies in small cell lung cancer (Review). Oncol Lett 2013, 5, 3–11.
- Okamoto I, Araki J, Suto R, Shimada M, Nakagawa K, Fukuoka M: EGFR mutation in gefitinib responsive small-cell lung cancer. Ann Oncol 2006, 17, 1028–1029.
- Zakowski MF, Ladanyi M, Kris MG: Memorial Sloan-Kettering Cancer Center Lung Cancer OncoGenome Group.: EGFR Mutations in Small-Cell Lung Cancers in Patients Who Have Never Smoked. N Engl J Med 2006, 355, 213–215.
- Moore AM, Einhorn LH, Estes D, Govindan R, Axelson J, Vinson J, Breen TE, Yu M, Hanna NH: Gefitinib in patients with chemo-sensitive and chemo-refractory relapsed small cell cancers: A Hoosier Oncology Group phase II trial. Lung Cancer 2006, 52, 93–97.
- Shiao TH, Chang YL, Yu CJ, Chang YC, Hsu YC, Chang SH, Shih JY, Yang PC: Epidermal growth factor receptor mutations in small cell lung cancer: A brief report. J Thorac Oncol 2011, 6, 195–198.
- Tatematsu A, Shimizu J, Murakami Y, Horio Y, Nakamura S, Hida T, Mitsudomi T, Yatabe1 Y: Epidermal growth factor receptor mutations in small cell lung cancer. Clin Cancer Res 2008, 14, 6092–6096.
- Lu HY, Sun WY, Chen B, Zhang YP, Cai JF, Su D, Wang Z, Zheng YQ, Ma SL: Epidermal growth factor receptor mutations in small cell lung cancer patients who received surgical resection in China. Neoplasma 2012, 59, 100–104.
- Lu HY, Lu ZY, Cheng QY, Cai JF, Wang XJ, Zhang YP, Lou CJ, Yu XM, Qin J, Ye WW, Lei L, Huang J, Yang HY, Mao WM: Identifying EGFR mutations from SCLC patient plasma by mutant-enriched liquidchip technology. Adv Clin Exp Med 2014, 23, 2.
- Lu HY, Mao WM, Cheng QY, Chen B, Cai JF, Wang XJ, Wang Z, Xie FJ: Mutation status of epidermal growth factor receptor and clinical features of patients with combined small cell lung cancer who received surgical treatment. Oncol lett 2012, 3, 1288–1292.
- Dy GK, Miller AA, Mandrekar SJ, Aubry MC, Langdon RM Jr, Morton RF, Schild SE, Jett JR, Adjei AA: A phase II trial of imatinib (ST1571) in patients with c-kit expressing relapsed small-cell lung cancer: A CALGB and NCCTG study. Ann Oncol 2005, 16, 1811–1816.
- Lu HY, Zhang G, Cheng QY, Chen B, Cai JF, Wang XJ, Zhang YP, Wang Z, Lu ZY, Xie FJ, Mao WM: Expression and mutation of the c-kit gene and correlation with prognosis of small cell lung cancer. Oncol Lett 2012, 4, 89–93.
- Hernandez-Ayaa LF, Gonzalez-Angulo AM: Targeting the phosphatidylinositol 3-kinase signaling pathway in breast cancer. Oncologist 2011, 16, 404–414.
- Song MS, Salmena L, Pandolfi PP: The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell 2012, 13, 283–296.
- Shibata T, Kokubu A, Tsuta K, Hirohashi S: Oncogenic mutation of PIK3CA in small cell lung carcinoma: A potential therapeutic target pathway for chemotherapy-resistant lung cancer. Cancer Lett 2009, 283, 203–211.
- Jackman DM, Johnson BE: Small-cell lung cancer. Lancet 2005, 366, 1385–1396.
- Sher T1, Dy GK, Adjei AA: Small cell lung cancer. Mayo Clin Proc 2008, 83, 355–367.
- Owonikoko T, Ramalingam S: Minimal progress, potential promise in small-cell lung cancer. Oncology 2008, 22, 1495–1496.
- Abidin AZ, Garassino MC, Califano R, Harle A, Blackhall F: Targeted therapies in small cell lung cancer: A review. Ther Adv Med Oncol 2010, 2, 25–37.
- Rostad H, Naalsund A, Jacobsen R, Strand TE, Scott H, Heyerdahl Strøm E, Norstein J: Small cell lung cancer in Norway. Should more patients have offered surgical therapy? Eur J Cardiothorac Surg 2004, 26, 782–786.
- Dillon RL, White DE, Muller WJ: The phosphatidyl inositol 3-kinase signaling network: Implications for human breast cancer. Oncogene 2007, 26, 1338–1345.
- Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B,Velculescu VE: High frequency of mutations of the PIK3CA gene in human cancers. Science 2004, 304–554.
- Qiu W, Schönleben F, Li X, Ho DJ: PIK3CA mutations in head and neck squamous cell carcinoma. Clin Cancer Res 2006, 12, 1441–1446.