Mutational status of PIK3ca oncogene in oral cancer-In the new age of PI3K inhibitors

被引:4
|
作者
Denninghoff, V [1 ,2 ,3 ]
Muino, A. [1 ]
Diaz, M. [1 ]
Harada, L. [1 ]
Lence, A. [1 ]
Turon, P. [1 ]
Labbrozzi, M. [1 ]
Aguas, S. [1 ]
Penaloza, P. [2 ]
Avagnina, A. [2 ]
Adler, I [1 ]
机构
[1] Univ Buenos Aires, Fac Dent, Stomatol, Buenos Aires, DF, Argentina
[2] Ctr Med Educ & Clin Res CEMIC, Pathol Dept, Buenos Aires, DF, Argentina
[3] Natl Sci & Tech Res Council CONICET, Buenos Aires, DF, Argentina
关键词
PI3K; Tongue; Oral cancer; SQUAMOUS-CELL CARCINOMA; HEAD; 3-KINASE; BIOLOGY; PATHWAY; GENE;
D O I
10.1016/j.prp.2019.152777
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
In the new age of PI3K inhibitors, the mutational status of PI3Kca oncogene in the Cavity Squamous Cell Carcinoma (OC-SCC) needs further analysis. It is the sixth most common cancer in the world. The aim of this study was to evaluate PI3Kca oncogene mutations and to correlate them with the clinical-histological characteristics of individuals presenting these tumors. We recruited 74 individuals with OC-SCC diagnosis (period 2000-2014). Histological sections were used. DNA was purified; PIK3ca gene exons 9 and 20 were amplified and sequenced. In 49/74 cases (66 %), the complete sequence of both codons was analyzed by Sanger method. We found that 7/49 (14 %) individuals mutated. In exon 9 we found 1/49 (2 %), and in exon 20 M1043I 8/49 (16 %). We have found the coexistence of more than one mutation in a same individual (E542 K and M1043I). A positive association was observed between the mutational status of the codon 9 (E542 K) and the tongue location. In conclusion, the frequency of PI3Kca gene mutation in OC-SCC was 16 %, which is similar to that reported for other populations. We found a mutation not previously described (M1043I) in this pathology. Should its biological effect be confirmed, it must be added to the list of PIK3ca mutations. Total mutations in the PIK3ca were 32 %, with tongue being the site at the greatest risk (E542K-E545K-M1043I). These findings would facilitate the identification of patients with therapeutic targets in the near future.
引用
收藏
页数:5
相关论文
共 50 条
  • [31] Comparative molecular dynamics analyses on PIK3CA hotspot mutations with PI3K alpha specific inhibitors and ATP
    Mentes, Muratcan
    Karakuzulu, Basak Buse
    Ucar, Gonlum Bahar
    Yandim, Cihangir
    [J]. COMPUTATIONAL BIOLOGY AND CHEMISTRY, 2022, 99
  • [32] Analysis of PIK3CA mutations and PI3K signaling proteins as prognostic biomarkers for advanced gastric cancer
    Nishizuka, Satoshi S.
    Ito, Chie
    Kume, Kohei
    Iwaya, Takeshi
    Koeda, Keisuke
    Sasaki, Akira
    [J]. CANCER RESEARCH, 2017, 77
  • [33] Screening for PIK3CA, RAS, and RAF mutations in trials with PI3K/AKT/mTOR signaling pathway inhibitors
    Janku, F.
    Tsimberidou, A. M.
    Garrido-Laguna, I.
    Hong, D. S.
    Naing, A. M.
    Falchook, G. S.
    Fu, S.
    Luthra, R.
    Wang, X.
    Kurzrock, R.
    [J]. EJC SUPPLEMENTS, 2010, 8 (07): : 83 - 83
  • [34] Activation of the PI3K/AKT pathway and PIK3CA mutations in Merkel cell carcinoma
    Hafner, C.
    Houben, R.
    Baeurle, A.
    Landthaler, M.
    Becker, J. C.
    [J]. JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, 2010, 8 (09): : 739 - 739
  • [35] EVALUATION OF PIK3CA MUTATIONAL STATUS IN GLIOMA MOLECULAR SUBGROUPS
    Brito, C.
    Azevedo, A.
    Esteves, S.
    Martins, C.
    Mafra, M.
    Roque, L.
    Pojo, M.
    [J]. NEURO-ONCOLOGY, 2019, 21 : 27 - 28
  • [36] Genetic alterations of PI3K/akt/mTOR pathway in urothelial carcinoma of urinary bladder: PIK3CA gene mutational analysis and PTEN expression status
    Netto, G. J.
    Cohen, J.
    Hansel, D.
    Hicks, J.
    Sidransky, D.
    Schoenberg, M.
    Jadallah, S.
    Murphy, K.
    [J]. JOURNAL OF MOLECULAR DIAGNOSTICS, 2007, 9 (05): : 691 - 691
  • [37] PIK3CA C2 Domain Deletions Hyperactivate Phosphoinositide 3-kinase (PI3K), Generate Oncogene Dependence, and Are Exquisitely Sensitive to PI3Kα Inhibitors (vol 24, pg 1426, 2018)
    Croessmann, Sarah
    Sheehan, Jonathan H.
    Lee, Kyung-min
    Sliwoski, Gregory
    He, Jie
    Nagy, Rebecca
    Riddle, David
    Mayer, Ingrid A.
    Balko, Justin M.
    Lanman, Richard
    Miller, Vincent A.
    Cantley, Lewis C.
    Meiler, Jens
    Arteaga, Carlos L.
    [J]. CLINICAL CANCER RESEARCH, 2019, 25 (04) : 1432 - 1432
  • [38] TRAF6 interacts with and ubiquitinates PIK3CA to enhance PI3K activation
    Wang, Zixi
    Liu, Yuxiang
    Huang, Song
    Fang, Min
    [J]. FEBS LETTERS, 2018, 592 (11): : 1882 - 1892
  • [39] Dual PI3K/mTOR Inhibition in Colorectal Cancers with APC and PIK3CA Mutations
    Foley, Tyler M.
    Payne, Susan N.
    Pasch, Cheri A.
    Yueh, Alex E.
    Van De Hey, Dana R.
    Korkos, Demetra P.
    Clipson, Linda
    Maher, Molly E.
    Matkowskyj, Kristina A.
    Newton, Michael A.
    Deming, Dustin A.
    [J]. MOLECULAR CANCER RESEARCH, 2017, 15 (03) : 317 - 327
  • [40] PIK3CA copy-number gain and inhibitors of the PI3K/AKT/mTOR pathway in triple-negative breast cancer
    Amato, Ottavia
    Buisseret, Laurence
    Gebhart, Geraldine
    Plouznikoff, Nicolas
    Larsimont, Denis
    Awada, Ahmad
    Piccart, Martine
    Aftimos, Philippe
    [J]. COLD SPRING HARBOR MOLECULAR CASE STUDIES, 2023, 9 (02):