Oncogenic mutations of PIK3CA in human cancers

Current Topics in Microbiology and Immunology

Volumn 347, Issue 1, 2010, Pages 21-41

  Samuels, Yardena ^a   Waldman, Todd ^b  

^a NATIONAL HUMAN GENOME RESEARCH INSTITUTE   (United States)

^b GEORGETOWN UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTHRACYCLINE; LAPATINIB; PACLITAXEL; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PIK3CA; TRASTUZUMAB; UNCLASSIFIED DRUG; PIK3CA PROTEIN, HUMAN;

ARTICLE; BILIARY TRACT CANCER; BRAIN TUMOR; BREAST CANCER; COLON CANCER; COLORECTAL CANCER; DISEASE ASSOCIATION; ENDOMETRIUM CANCER; ENZYME ACTIVE SITE; ESOPHAGUS CANCER; GENE FUNCTION; GENE IDENTIFICATION; GENE MUTATION; GENE PRODUCT; HEAD AND NECK CANCER; HIGH THROUGHPUT SCREENING; HUMAN; HYPOPHYSIS TUMOR; LIVER CANCER; LUNG CANCER; LYMPHOMA; MISSENSE MUTATION; MULTIGENE FAMILY; NEOPLASM; NEUROBLASTOMA; ONCOGENE; OVARY CANCER; PANCREAS CANCER; PRIORITY JOURNAL; SKIN CANCER; SOMATIC MUTATION; STOMACH CANCER; THYROID CANCER; URINARY TRACT CANCER; UTERINE CERVIX CANCER; ENZYMOLOGY; GENETICS; MUTATION; PHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION;

HUMANS; MUTATION; NEOPLASMS; PHOSPHATIDYLINOSITOL 3-KINASES; SIGNAL TRANSDUCTION;

EID: 79952108510     PISSN: 0070217X     EISSN: None     Source Type: Book Series    
DOI: 10.1007/82-2010-68     Document Type: Article

References (140)

1. Abubaker J, Bavi PP, Al-Harbi S, Siraj AK, Al-Dayel F, Uddin S, Al-Kuraya K (2007) PIK3CA mutations are mutually exclusive with PTEN loss in diffuse large B-cell lymphoma. Leukemia 21:2368-2370 (Pubitemid 350011714)
2. Abubaker J, Bavi P, Al-Harbi S, Ibrahim M, Siraj AK, Al-Sanea N, Abduljabbar A, Ashari LH, Alhomoud S, Al-Dayel F et al (2008a) Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population. Oncogene 27:3539-3545 (Pubitemid 351793794)
3. Abubaker J, Jehan Z, Bavi P, Sultana M, Al-Harbi S, Ibrahim M, Al-Nuaim A, Ahmed M, Amin T, Al-Fehaily M et al (2008b) Clinicopathological analysis of papillary thyroid cancer with PIK3CA alterations in a Middle Eastern population. J Clin Endocrinol Metab 93:611-618 (Pubitemid 351240838)
4. Actor B, Cobbers JM, Buschges R, Wolter M, Knobbe CB, Lichter P, Reifenberger G, Weber RG (2002) Comprehensive analysis of genomic alterations in gliosarcoma and its two tissue components. Genes Chromosomes Cancer 34:416-427 (Pubitemid 34787463)
5. Akagi I, Miyashita M, Makino H, Nomura T, Hagiwara N, Takahashi K, Cho K, Mishima T, Ishibashi O, Ushijima T et al (2009) Overexpression of PIK3CA is associated with lymph node metastasis in esophageal squamous cell carcinoma. Int J Oncol 34:767-775
6. Andersson P, Kolaric A, Windahl T, Kirrander P, Soderkvist P, Karlsson MG (2008) PIK3CA, HRAS and KRAS gene mutations in human penile cancer. J Urol 179:2030-2034
7. Bachman KE, Argani P, Samuels Y, Silliman N, Ptak J, Szabo S, Konishi H, Karakas B, Blair BG, Lin C et al (2004) The PIK3CA gene is mutated with high frequency in human breast cancers. Cancer Biol Ther 3:772-775 (Pubitemid 41351083)
8. Bader AG, Kang S, Vogt PK (2006) Cancer-specific mutations in PIK3CA are oncogenic in vivo. Proc Natl Acad Sci USA 103:1475-1479 (Pubitemid 43191190)
9. Barault L, Veyrie N, Jooste V, Lecorre D, Chapusot C, Ferraz JM, Lievre A, Cortet M, Bouvier AM, Rat P et al (2008) Mutations in the RAS-MAPK, PI(3)K (phosphatidylinositol-3-OH kinase) signaling network correlate with poor survival in a population-based series of colon cancers. Int J Cancer 122:2255-2259 (Pubitemid 351542328)
10. Barbareschi M, Buttitta F, Felicioni L, Cotrupi S, Barassi F, Del Grammastro M, Ferro A, Dalla Palma P, Galligioni E, Marchetti A (2007) Different prognostic roles of mutations in the helical and kinase domains of the PIK3CA gene in breast carcinomas. Clin Cancer Res 13:6064-6069 (Pubitemid 350075063)
11. Bardelli A, Parsons DW, Silliman N, Ptak J, Szabo S, Saha S, Markowitz S, Willson JK, Parmigiani G, Kinzler KW et al (2003) Mutational analysis of the tyrosine kinome in colorectal cancers. Science 300:949 (Pubitemid 36548874)
12. Barr FG, Galili N, Holick J, Biegel JA, Rovera G, Emanuel BS (1993) Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma. Nat Genet 3:113-117 (Pubitemid 23079791)
13. Bastian BC, LeBoit PE, Hamm H, Brocker EB, Pinkel D (1998) Chromosomal gains and losses in primary cutaneous melanomas detected by comparative genomic hybridization. Cancer Res 58:2170-2175 (Pubitemid 28232904)
14. Bellacosa A, Testa JR, Staal SP, Tsichlis PN (1991) A retroviral oncogene, akt, encoding a serinethreonine kinase containing an SH2-like region. Science 254:274-277 (Pubitemid 21917339)
15. Bellacosa A, de Feo D, Godwin AK, Bell DW, Cheng JQ, Altomare DA, Wan M, Dubeau L, Scambia G, Masciullo V et al (1995) Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas. Int J Cancer 64:280-285
16. Benvenuti S, Frattini M, Arena S, Zanon C, Cappelletti V, Coradini D, Daidone MG, Pilotti S, Pierotti MA, Bardelli A (2008) PIK3CA cancer mutations display gender and tissue specificity patterns. Hum Mutat 29:284-288 (Pubitemid 351240601)
17. Berns K, Horlings HM, Hennessy BT, Madiredjo M, Hijmans EM, Beelen K, Linn SC, Gonzalez-Angulo AM, Stemke-Hale K, Hauptmann M et al (2007) A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell 12:395-402 (Pubitemid 47539306)
18. Birck A, Ahrenkiel V, Zeuthen J, Hou-Jensen K, Guldberg P (2000) Mutation and allelic loss of the PTEN/MMAC1 gene in primary and metastatic melanoma biopsies. J Invest Dermatol 114:277-280 (Pubitemid 30417761)
19. Bleeker FE, Felicioni L, Buttitta F, Lamba S, Cardone L, Rodolfo M, Scarpa A, Leenstra S, Frattini M, Barbareschi M et al (2008) AKT1(E17K) in human solid tumours. Oncogene 27:5648-5650
20. Board RE, Thelwell NJ, Ravetto PF, Little S, Ranson M, Dive C, Hughes A, Whitcombe D (2008) Multiplexed assays for detection of mutations in PIK3CA. Clin Chem 54:757-760 (Pubitemid 351573719)
21. Bos JL, Fearon ER, Hamilton SR, Verlaan-de Vries M, van Boom JH, van der Eb AJ, Vogelstein B (1987) Prevalence of ras gene mutations in human colorectal cancers. Nature 327:293-297 (Pubitemid 17075079)
22. Broderick DK,Di C, Parrett TJ, Samuels YR, Cummins JM,McLendon RE, Fults DW,VelculescuVE, Bigner DD, Yan H (2004) Mutations of PIK3CA in anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas. Cancer Res 64:5048-5050 (Pubitemid 39006515)
23. Buttitta F, Felicioni L, Barassi F, Martella C, Paolizzi D, Fresu G, Salvatore S, Cuccurullo F, Mezzetti A, Campani D, Marchetti A (2006) PIK3CA mutation and histological type in breast carcinoma: high frequency of mutations in lobular carcinoma. J Pathol 208:350-355 (Pubitemid 43210521)
24. Byun DS, Cho K, Ryu BK, Lee MG, Park JI, Chae KS, Kim HJ, Chi SG (2003) Frequent monoallelic deletion of PTEN and its reciprocal associatioin with PIK3CA amplification in gastric carcinoma. Int J Cancer 104:318-327 (Pubitemid 36249814)
25. Campbell IG, Russell SE, Choong DY, Montgomery KG, Ciavarella ML, Hooi CS, Cristiano BE, Pearson RB, Phillips WA (2004) Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res 64:7678-7681 (Pubitemid 39446895)
26. Cancer Genome Atlas Research Network (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061-1068
27. Cantley LC (2002) The phosphoinositide 3-kinase pathway. Science 296:1655-1657 (Pubitemid 34579158)
28. Cantley LC, Auger KR, Carpenter C, Duckworth B, Graziani A, Kapeller R, Soltoff S (1991) Oncogenes and signal transduction. Cell 64:281-302 (Pubitemid 121001255)
29. Carpten JD, Faber AL, Horn C, Donoho GP, Briggs SL, Robbins CM, Hostetter G, Boguslawski S, Moses TY, Savage S et al (2007) A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature 448:439-444 (Pubitemid 47123510)
30. Catasus L, Gallardo A, Cuatrecasas M, Prat J (2008) PIK3CA mutations in the kinase domain (exon 20) of uterine endometrial adenocarcinomas are associated with adverse prognostic parameters. Mod Pathol 21:131-139 (Pubitemid 351172164)
31. Chang HW, Aoki M, Fruman D, Auger KR, Bellacosa A, Tsichlis PN, Cantley LC, Roberts TM, Vogt PK (1997) Transformation of chicken cells by the gene encoding the catalytic subunit of PI 3-kinase. Science 276:1848-1850 (Pubitemid 27443659)
32. Chen Z, Trotman LC, Shaffer D, Lin HK, Dotan ZA, Niki M, Koutcher JA, Scher HI, Ludwig T, Gerald W et al (2005) Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 436:725-730 (Pubitemid 41117277)
33. Cheng JQ, Godwin AK, Bellacosa A, Taguchi T, Franke TF, Hamilton TC, Tsichlis PN, Testa JR (1992) AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/ threonine kinases, is amplified in human ovarian carcinomas. Proc Natl Acad Sci USA 89:9267-9271
34. Cheng JQ, Ruggeri B, Klein WM, Sonoda G, Altomare DA, Watson DK, Testa JR (1996) Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA. Proc Natl Acad Sci USA 93:3636-3641 (Pubitemid 26127592)
35. Chou CC, Chou MJ, Tzen CY (2008) PIK3CA mutation occurs in nasopharyngeal carcinoma but does not significantly influence the disease-specific survival. Med Oncol 26(3):322-326
36. Chudnovsky Y, Khavari PA, Adams AE (2005) Melanoma genetics and the development of rational therapeutics. J Clin Invest 115:813-824 (Pubitemid 40489381)
37. Cui B, Zheng B, Zhang X, Stendahl U, Andersson S, Wallin KL (2009) Mutation of PIK3CA: possible risk factor for cervical carcinogenesis in older women. Int J Oncol 34:409-416
38. Dam V, Morgan BT, Mazanek P, Hogarty MD (2006) Mutations in PIK3CA are infrequent in neuroblastoma. BMC Cancer 6:177
39. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W et al (2002) Mutations of the BRAF gene in human cancer. Nature 417 (6892):949-954 (Pubitemid 34716871)
40. Eichhorn PJ, Gili M, Scaltriti M, Serra V, Guzman M, Nijkamp W, Beijersbergen RL, Valero V, Seoane J, Bernards R, Baselga J (2008) Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235. Cancer Res 68:9221-9230
41. Fenic I, Steger K, Gruber C, Arens C, Woenckhaus J (2007) Analysis of PIK3CA and Akt/protein kinase B in head and neck squamous cell carcinoma. Oncol Rep 18:253-259
42. Gallia GL, Rand V, Siu IM, Eberhart CG, James CD, Marie SK, Oba-Shinjo SM, Carlotti CG, Caballero OL, Simpson AJ et al (2006) PIK3CA gene mutations in pediatric and adult glioblastoma multiforme. Mol Cancer Res 4:709-714 (Pubitemid 44683311)
43. Garcia-Rostan G, Costa AM, Pereira-Castro I, Salvatore G, Hernandez R, Hermsem MJ, Herrero A, Fusco A, Cameselle-Teijeiro J, Santoro M (2005) Mutation of the PIK3CA gene in anaplastic thyroid cancer. Cancer Res 65:10199-10207 (Pubitemid 41743711)
44. Guldberg P, thor Straten P, Birck A, Ahrenkiel V, Kirkin AF, Zeuthen J (1997) Disruption of the MMAC1/PTEN gene by deletion or mutation is a frequent event in malignant melanoma. Cancer Res 57:3660-3663 (Pubitemid 27381203)
45. Hafner C, Lopez-Knowles E, Luis NM, Toll A, Baselga E, Fernandez-Casado A, Hernandez S, Ribe A, Mentzel T, Stoehr R et al (2007) Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern. Proc Natl Acad Sci USA 104:13450-13454 (Pubitemid 47293965)
46. Hafner C, Vogt T, Landthaler M, Musebeck J (2008) Somatic FGFR3 and PIK3CA mutations are present in familial seborrhoeic keratoses. Br J Dermatol 159:214-217 (Pubitemid 351874504)
47. Hafner C, Stoehr R, van Oers JM, Zwarthoff EC, Hofstaedter F, Landthaler M, Hartmann A, Vogt T (2009) FGFR3 and PIK3CA mutations are involved in the molecular pathogenesis of solar lentigo. Br J Dermatol 160:546-551
48. Hartmann C, Bartels G, Gehlhaar C, Holtkamp N, von Deimling A (2005) PIK3CA mutations in glioblastoma multiforme. Acta Neuropathol 109:639-642 (Pubitemid 40974153)
49. Hartmann C, Devermann L, Gehlhaar C, Holtkamp N, von Deimling A (2006) PIK3CA mutations in oligodendroglial tumours. Neuropathol Appl Neurobiol 32:209-212
50. Hayes MP, Wang H, Espinal-Witter R, Douglas W, Solomon GJ, Baker SJ, Ellenson LH (2006) PIK3CA and PTEN mutations in uterine endometrioid carcinoma and complex atypical hyperplasia. Clin Cancer Res 12:5932-5935 (Pubitemid 44703751)
51. Hayes MP, Douglas W, Ellenson LH (2009) Molecular alterations of EGFR and PIK3CA in uterine serous carcinoma. Gynecol Oncol 113(3):370-373
52. Hummerdal P, Andersson P, Willander K, Linderholm M, Soderkvist P, Jonsson JI (2006) Absence of hot spot mutations of the PIK3CA gene in acute myeloid leukaemia. Eur J Haematol 77:86-87 (Pubitemid 43876212)
53. Jen J, Powell SM, Papadopoulos N, Smith KJ, Hamilton SR, Vogelstein B, Kinzler KW (1994) Molecular determinants of dysplasia in colorectal lesions. Cancer Res 54:5523-5526 (Pubitemid 24346238)
54. Jhawer M, Goel S, Wilson AJ, Montagna C, Ling YH, Byun DS, Nasser S, Arango D, Shin J, Klampfer L et al (2008) PIK3CA mutation/PTEN expression status predicts response of colon cancer cells to the epidermal growth factor receptor inhibitor cetuximab. Cancer Res 68:1953-1961 (Pubitemid 351416582)
55. Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A et al (2008) Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321:1801-1806
56. Kang S, Bader AG, Vogt PK (2005) Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic. Proc Natl Acad Sci USA 102:802-807 (Pubitemid 40282746)
57. Kang S, Seo SS, Chang HJ, Yoo CW, Park SY, Dong SM (2008) Mutual exclusiveness between PIK3CA and KRAS mutations in endometrial carcinoma. Int J Gynecol Cancer 18:1339-1343
58. Kato S, Iida S, Higuchi T, Ishikawa T, Takagi Y, Yasuno M, Enomoto M, Uetake H, Sugihara K (2007) PIK3CA mutation is predictive of poor survival in patients with colorectal cancer. Int J Cancer 121:1771-1778 (Pubitemid 47417296)
59. Katso R, Okkenhaug K, Ahmadi K, White S, Timms J, Waterfield MD (2001) Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Annu Rev Cell Dev Biol 17:615-675 (Pubitemid 33096187)
60. Kawano O, Sasaki H, Endo K, Suzuki E, Haneda H, Yukiue H, Kobayashi Y, Yano M, Fujii Y (2006) PIK3CA mutation status in Japanese lung cancer patients. Lung Cancer 54:209-215 (Pubitemid 44764916)
61. Kawano O, Sasaki H, Okuda K, Yukiue H, Yokoyama T, Yano M, Fujii Y (2007) PIK3CA gene amplification in Japanese non-small cell lung cancer. Lung Cancer 58:159-160 (Pubitemid 47379973)
62. Kim JS, Lee C, Bonifant CL, Ressom H, Waldman T (2007) Activation of p53-dependent growth suppression in human cells by mutations in PTEN or PIK3CA. Mol Cell Biol 27:662-677 (Pubitemid 46080132)
63. Kita D, Yonekawa Y, Weller M, Ohgaki H (2007) PIK3CA alterations in primary (de novo) and secondary glioblastomas. Acta Neuropathol 113:295-302 (Pubitemid 46443564)
64. Knobbe CB, Reifenberger G (2003) Genetic alterations and aberrant expression of genes related to the phosphatidyl-inositol-30-kinase/protein kinase B (Akt) signal transduction pathway in glioblastomas. Brain Pathol 13:507-518 (Pubitemid 37420695)
65. Knobbe CB, Trampe-Kieslich A, Reifenberger G (2005) Genetic alteration and expression of the phosphoinositol-3-kinase/Akt pathway genes PIK3CA and PIKE in human glioblastomas. Neuropathol Appl Neurobiol 31:486-490 (Pubitemid 41337782)
66. Kolasa IK, Rembiszewska A, Felisiak A, Ziolkowska-Seta I, Murawska M, Moes J, Timorek A, Dansonka-Mieszkowska A, Kupryjanczyk J (2009) PIK3CA amplification associates with resistance to chemotherapy in ovarian cancer patients. Cancer Biol Ther 8:21-26
67. Kozaki K, Imoto I, Pimkhaokham A, Hasegawa S, Tsuda H, Omura K, Inazawa J (2006) PIK3CA mutation is an oncogenic aberration at advanced stages of oral squamous cell carcinoma. Cancer Sci 97:1351-1358 (Pubitemid 44614987)
68. Lai YL, Mau BL, Cheng WH, Chen HM, Chiu HH, Tzen CY (2008) PIK3CA exon 20 mutation is independently associated with a poor prognosis in breast cancer patients. Ann Surg Oncol 15:1064-1069
69. Lee JW, Soung YH, Kim SY, Lee HW, Park WS, Nam SW, Kim SH, Lee JY, Yoo NJ, Lee SH (2005) PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. Oncogene 24:1477-1480 (Pubitemid 40343128)
70. Lerma E, Catasus L, Gallardo A, Peiro G, Alonso C, Aranda I, Barnadas A, Prat J (2008) Exon 20 PIK3CA mutations decreases survival in aggressive (HER-2 positive) breast carcinomas. Virchows Arch 453:133-139
71. Levine DA, Bogomolniy F, Yee CJ, Lash A, Barakat RR, Borgen PI, Boyd J (2005) Frequent mutation of the PIK3CA gene in ovarian and breast cancers. Clin Cancer Res 11:2875-2878 (Pubitemid 40525186)
72. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L,McCombie R et al (1997) PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275:1943-1947 (Pubitemid 27148818)
73. Li VS, Wong CW, Chan TL, Chan AS, Zhao W, Chu KM, So S, Chen X, Yuen ST, Leung SY (2005) Mutations of PIK3CA in gastric adenocarcinoma. BMC Cancer 5:29
74. Li SY, Rong M, Grieu F, Iacopetta B (2006) PIK3CA mutations in breast cancer are associated with poor outcome. Breast Cancer Res Treat 96:91-95
75. Liedtke C, Cardone L, Tordai A, Yan K, Gomez HL, Figureoa LJ, Hubbard RE, Valero V, Souchon EA, Symmans WF et al (2008) PIK3CA-activating mutations and chemotherapy sensitivity in stage II-III breast cancer. Breast Cancer Res 10:R27
76. Lin Y, Jiang X, Shen Y, Li M, Ma H, Xing M, Lu Y (2009) Frequent mutations and amplifications of the PIK3CA gene in pituitary tumors. Endocr Relat Cancer 16:301-310
77. Liu P, Li DJ, Qin HD, Zhang RH, Chen LZ, Zeng YX (2007) Screening for mutations in the hotspot mutation regions of PIK3CA gene in nasopharyngeal carcinoma. Ai Zheng 26:15-20
78. Lopez-Knowles E, Hernandez S, Malats N, Kogevinas M, Lloreta J, Carrato A, Tardon A, Serra C, Real FX (2006) PIK3CA mutations are an early genetic alteration associated with FGFR3 mutations in superficial papillary bladder tumors. Cancer Res 66:7401-7404 (Pubitemid 44289191)
79. Ma YY, Wei SJ, Lin YC, Lung JC, Chang TC, Whang-Peng J, Liu JM, Yang DM, Yang WK, Shen CY (2000) PIK3CA as an oncogene in cervical cancer. Oncogene 19:2739-2744 (Pubitemid 30339223)
80. Maruyama N, Miyoshi Y, Taguchi T, Tamaki Y, Monden M, Noguchi S (2007) Clinicopathologic analysis of breast cancers with PIK3CA mutations in Japanese women. Clin Cancer Res 13:408-414 (Pubitemid 46225343)
81. Massion PP, Taflan PM, Shyr Y, Rahman SM, Yildiz P, Shakthour B, Edgerton ME, Ninan M, Andersen JJ, Gonzalez AL (2004) Early involvement of the phosphatidylinositol 3-kinase/Akt pathway in lung cancer progression. Am J Respir Crit Care Med 170:1088-1094 (Pubitemid 39488621)
82. Mikami M, Nosho K, Yamamoto H, Takahashi T, Maehata T, Taniguchi H, Adachi Y, Imamura A, Fujita M, Hosokawa M et al (2006) Mutational analysis of beta-catenin and the RAS-RAF signalling pathway in early flat-type colorectal tumours. Eur J Cancer 42:3065-3072 (Pubitemid 44667483)
83. Miyake T, Yoshino K, Enomoto T, Takata T, Ugaki H, Kim A, Fujiwara K, Miyatake T, Fujita M, Kimura T (2008) PIK3CA gene mutations and amplifications in uterine cancers, identified by methods that avoid confounding by PIK3CA pseudogene sequences. Cancer Lett 261:120-126
84. Miyaki M, Iijima T, Yamaguchi T, Takahashi K, Matsumoto H, Yasutome M, Funata N, Mori T (2007) Mutations of the PIK3CA gene in hereditary colorectal cancers. Int J Cancer 121:1627-1630 (Pubitemid 47328725)
85. Mori R, Ishiguro H, Kimura M, Mitsui A, Sasaki H, Tomoda K, Mori Y, Ogawa R, Katada T, Kawano O et al (2008) PIK3CA mutation status in Japanese esophageal squamous cell carcinoma. J Surg Res 145:320-326
86. Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, Kinzler KW (1997) Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science 275:1787-1790 (Pubitemid 27136715)
87. Mueller W, Mizoguchi M, Silen E, D'Amore K, Nutt CL, Louis DN (2005) Mutations of the PIK3CA gene are rare in human glioblastoma. Acta Neuropathol 109:654-655 (Pubitemid 40974155)
88. Muller CI, Miller CW, Hofmann WK, Gross ME, Walsh CS, Kawamata N, Luong QT, Koeffler HP (2007) Rare mutations of the PIK3CA gene in malignancies of the hematopoietic system as well as endometrium, ovary, prostate and osteosarcomas, and discovery of a PIK3CA pseudogene. Leuk Res 31:27-32 (Pubitemid 44709746)
89. Murugan AK, Hong NT, Fukui Y, Munirajan AK, Tsuchida N (2008) Oncogenic mutations of the PIK3CA gene in head and neck squamous cell carcinomas. Int J Oncol 32:101-111 (Pubitemid 351176067)
90. Nakayama K, Nakayama N, Kurman RJ, Cope L, Pohl G, Samuels Y, Velculescu VE, Wang TL, Shih Ie M (2006) Sequence mutations and amplification of PIK3CA and AKT2 genes in purified ovarian serous neoplasms. Cancer Biol Ther 5:779-785 (Pubitemid 44775134)
91. Oda K, Stokoe D, Taketani Y, McCormick F (2005) High frequency of coexistent mutations of PIK3CA and PTEN genes in endometrial carcinoma. Cancer Res 65:10669-10673 (Pubitemid 41713332)
92. Ogino S, Nosho K, Kirkner GJ, Shima K, Irahara N, Kure S, Chan AT, Engelman JA, Kraft P, Cantley LC et al (2009) PIK3CA mutation is associated with poor prognosis among patients with curatively resected colon cancer. J Clin Oncol 27:1477-1484
93. Okudela K, Suzuki M, Kageyama S, Bunai T, Nagura K, Igarashi H, Takamochi K, Suzuki K, Yamada T, Niwa H et al (2007) PIK3CA mutation and amplification in human lung cancer. Pathol Int 57:664-671 (Pubitemid 47353042)
94. Ollikainen M, Gylling A, Puputti M, Nupponen NN, Abdel-Rahman WM, Butzow R, Peltomaki P (2007) Patterns of PIK3CA alterations in familial colorectal and endometrial carcinoma. Int J Cancer 121:915-920 (Pubitemid 47106226)
95. Omholt K, Krockel D, Ringborg U, Hansson J (2006) Mutations of PIK3CA are rare in cutaneous melanoma. Melanoma Res 16:197-200 (Pubitemid 44090052)
96. Or YY, Hui AB, To KF, Lam CN, Lo KW (2006) PIK3CA mutations in nasopharyngeal carcinoma. Int J Cancer 118:1065-1067
97. Page C, Huang M, Jin X, Cho K, Lilja J, Reynolds RK, Lin J (2000) Elevated phosphorylation of AKT and Stat3 in prostate, breast, and cervical cancer cells. Int J Oncol 17:23-28
98. Pang JC, Chung NY, Chan NH, Poon WS, Thomas T, Ng HK (2006) Rare mutation of PIK3CA in meningiomas. Acta Neuropathol 111:284-285
99. Parsons DW, Wang TL, Samuels Y, Bardelli A, Cummins JM, DeLong L, Silliman N, Ptak J, Szabo S, Willson JK et al (2005) Colorectal cancer: mutations in a signalling pathway. Nature 436:792 (Pubitemid 41160630)
100. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807-1812
101. Perez-Tenorio G, Alkhori L, Olsson B, Waltersson MA, Nordenskjold B, Rutqvist LE, Skoog L, Stal O (2007) PIK3CA mutations and PTEN loss correlate with similar prognostic factors and are not mutually exclusive in breast cancer. Clin Cancer Res 13:3577-3584 (Pubitemid 46955118)
102. Phillips WA, Russell SE, Ciavarella ML, Choong DY, Montgomery KG, Smith K, Pearson RB, Thomas RJ, Campbell IG (2006) Mutation analysis of PIK3CA and PIK3CB in esophageal cancer and Barrett's esophagus. Int J Cancer 118:2644-2646
103. Philp AJ, Campbell IG, Leet C, Vincan E, Rockman SP, Whitehead RH, Thomas RJ, Phillips WA (2001) The phosphatidylinositol 30-kinase p85alpha gene is an oncogene in human ovarian and colon tumors. Cancer Res 61:7426-7429 (Pubitemid 32995029)
104. Qiu W, Schonleben F, Li X, Ho DJ, Close LG, Manolidis S, Bennett BP, Su GH (2006) PIK3CA mutations in head and neck squamous cell carcinoma. Clin Cancer Res 12:1441-1446
105. Qiu W, Tong GX, Manolidis S, Close LG, Assaad AM, Su GH (2008) Novel mutant-enriched sequencing identified high frequency of PIK3CA mutations in pharyngeal cancer. Int J Cancer 122:1189-1194 (Pubitemid 351214020)
106. Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE (2002) Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature 418:934 (Pubitemid 34976022)
107. Riener MO, Bawohl M, Clavien PA, Jochum W (2008) Rare PIK3CA hotspot mutations in carcinomas of the biliary tract. Genes Chromosomes Cancer 47:363-367 (Pubitemid 351451790)
108. Robertson GP, Furnari FB, MieleME, Glendening MJ,Welch DR, Fountain JW, Lugo TG, Huang HJ, CaveneeWK (1998) In vitro loss of heterozygosity targets the PTEN/MMAC1 gene in melanoma. Proc Natl Acad Sci USA 95:9418-9423 (Pubitemid 28506246)
109. Saal LH, Holm K, Maurer M, Memeo L, Su T, Wang X, Yu JS, Malmstrom PO, Mansukhani M, Enoksson J et al (2005) PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res 65:2554-2559 (Pubitemid 40490050)
110. Saal LH, Johansson P, Holm K, Gruvberger-Saal SK, She QB, Maurer M, Koujak S, Ferrando AA, Malmstrom P, Memeo L et al (2007) Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proc Natl Acad Sci USA 104:7564-7569 (Pubitemid 47185946)
111. Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ et al (2004) High frequency of mutations of the PIK3CA gene in human cancers. Science 304:554 (Pubitemid 38541907)
112. Samuels Y, Diaz LA Jr., Schmidt-Kittler O, Cummins JM, Delong L, Cheong I, Rago C, Huso DL, Lengauer C, Kinzler KW et al (2005) Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell 7:561-573 (Pubitemid 40799249)
113. Santarpia L, El-Naggar AK, Cote GJ, Myers JN, Sherman SI (2008) Phosphatidylinositol 3-kinase/ akt and ras/raf-mitogen-activated protein kinase pathway mutations in anaplastic thyroid cancer. J Clin Endocrinol Metab 93:278-284
114. Sartore-Bianchi A, Martini M, Molinari F, Veronese S, Nichelatti M, Artale S, Di Nicolantonio F, Saletti P, De Dosso S, Mazzucchelli L et al (2009) PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res 69:1851-1857
115. Schonleben F, Qiu W, Ciau NT, Ho DJ, Li X, Allendorf JD, Remotti HE, Su GH (2006) PIK3CA mutations in intraductal papillary mucinous neoplasm/carcinoma of the pancreas. Clin Cancer Res 12:3851-3855 (Pubitemid 44000267)
116. Sharma SV, Bell DW, Settleman J, Haber DA (2007) Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 7:169-181
117. Shayesteh L, Lu Y, Kuo WL, Baldocchi R, Godfrey T, Collins C, Pinkel D, Powell B, Mills GB, Gray JW (1999) PIK3CA is implicated as an oncogene in ovarian cancer. Nat Genet 21:99-102 (Pubitemid 29036292)
118. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N et al (2006) The consensus coding sequences of human breast and colorectal cancers. Science 314:268-274 (Pubitemid 44571966)
119. Sparks AB, Morin PJ, Vogelstein B, Kinzler KW (1998) Mutational Analysis of the APC/bcatenin/ Tcf Pathway in Colorectal Cancer. Cancer Res 58:1130-1134 (Pubitemid 28183198)
120. Staal SP (1987) Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma. Proc Natl Acad Sci USA 84:5034-5037 (Pubitemid 17095859)
121. Stahl JM, Sharma A, Cheung M, Zimmerman M, Cheng JQ, Bosenberg MW, Kester M, Sandirasegarane L, Robertson GP (2004) Deregulated Akt3 activity promotes development of malignant melanoma. Cancer Res 64:7002-7010 (Pubitemid 39331010)
122. Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T et al (1997) Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet 15:356-362 (Pubitemid 27147102)
123. Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, Neve RM, Kuo WL, Davies M, Carey M, Hu Z, Guan Y, Sahin A et al (2008) An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res 68:6084-6091
124. Stephens M, Sloan JS, Robertson PD, Scheet P, Nickerson DA (2006) Automating sequence-based detection and genotyping of SNPs from diploid samples. Nat Genet 38:375-381
125. Tanaka Y, Kanai F, Tada M, Asaoka Y, Guleng B, Jazag A, Ohta M, Ikenoue T, Tateishi K, Obi S et al (2006) Absence of PIK3CA hotspot mutations in hepatocellular carcinoma in Japanese patients. Oncogene 25:2950-2952 (Pubitemid 43739246)
126. Thompson FH, Emerson J, Olson S, Weinstein R, Leavitt SA, Leong SP, Emerson S, Trent JM, Nelson MA, Salmon SE et al (1995) Cytogenetics of 158 patients with regional or disseminated melanoma. Subset analysis of near-diploid and simple karyotypes. Cancer Genet Cytogenet 83:93-104
127. Tsao H, Zhang X, Benoit E, Haluska FG (1998) Identification of PTEN/MMAC1 alterations in uncultured melanomas and melanoma cell lines. Oncogene 16:3397-3402 (Pubitemid 28349682)
128. Vanhaesebroeck B, Waterfield MD (1999) Signaling by distinct classes of phosphoinositide 3-kinases. Exp Cell Res 253:239-254
129. Velasco A, Bussaglia E, Pallares J, Dolcet X, Llobet D, Encinas M, Llecha N, Palacios J, Prat J, Matias-Guiu X (2006) PIK3CA gene mutations in endometrial carcinoma: correlation with PTEN and K-RAS alterations. Hum Pathol 37:1465-1472 (Pubitemid 44584324)
130. Velho S, Oliveira C, Ferreira A, Ferreira AC, Suriano G, Schwartz S Jr., Duval A, Carneiro F, Machado JC, Hamelin R, Seruca R (2005) The prevalence of PIK3CA mutations in gastric and colon cancer. Eur J Cancer 41:1649-1654 (Pubitemid 40981849)
131. Vivanco I, Sawyers CL (2002) The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2:489-501 (Pubitemid 37328931)
132. Wang Y, Helland A, Holm R, Kristensen GB, Borresen-Dale AL (2005) PIK3CA mutations in advanced ovarian carcinomas. Hum Mutat 25:322
133. Wang Y, Hou P, Yu H, Wang W, Ji M, Zhao S, Yan S, Sun X, Liu D, Shi B et al (2007) High prevalence and mutual exclusivity of genetic alterations in the phosphatidylinositol-3-kinase/ akt pathway in thyroid tumors. J Clin Endocrinol Metab 92:2387-2390 (Pubitemid 46997152)
134. Wood LD, Parsons DW, Jones S, Lin J, Sjoblom T, Leary RJ, Shen D, Boca SM, Barber T, Ptak J et al (2007) The genomic landscapes of human breast and colorectal cancers. Science 318 (5853):1108-1113 (Pubitemid 350134889)
135. Wu G, Mambo E, Guo Z, Hu S, Huang X, Gollin SM, Trink B, Ladenson PW, Sidransky D, XingM (2005a) Uncommon mutation, but common amplifications, of the PIK3CA gene in thyroid tumors. J Clin Endocrinol Metab 90:4688-4693 (Pubitemid 41159359)
136. Wu G, Xing M, Mambo E, Huang X, Liu J, Guo Z, Chatterjee A, Goldenberg D, Gollin SM, Sukumar S et al (2005b) Somatic mutation and gain of copy number of PIK3CA in human breast cancer. Breast Cancer Res 7:R609-R616
137. Yamamoto H, Shigematsu H, Nomura M, Lockwood WW, Sato M, Okumura N, Soh
138. Zhang L, Yang N, Katsaros D, Huang W, Park JW, Fracchioli S, Vezzani C, Rigault de la Longrais IA, YaoW, Rubin SC, Coukos G (2003) The oncogene phosphatidylinositol 30-kinase catalytic subunit alpha promotes angiogenesis via vascular endothelial growth factor in ovarian carcinoma. Cancer Res 63:4225-4231 (Pubitemid 36917950)
139. Zhao L, Vogt PK (2008) Helical domain and kinase domain mutations in p110alpha of phosphatidylinositol 3-kinase induce gain of function by different mechanisms. Proc Natl Acad Sci USA 105:2652-2657 (Pubitemid 351520568)
140. Zhou XP, Gimm O, Hampel H, Niemann T, Walker MJ, Eng C (2000) Epigenetic PTEN silencing in malignant melanomas without PTEN mutation. Am J Pathol 157:1123-1128