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PTEN
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Interpretation 2289
Tier 2
PTEN
Variants
PTEN I101T
Primary Sites
Thyroid
Tumor Types
Papillary Carcinoma
Interpretation

PTEN is an obligate haplo-insufficient tumor suppressor gene and is mutated in a large number of cancers. It encodes a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/mTOR signaling pathway. Cancer-associated alterations in this gene often result in loss of PTEN protein and upregulation of the PI3K/AKT/mTOR pathway. PTEN mutations have been reported in 15% of anaplastic thyroid cancer. Germline mutations of PTEN lead to inherited hamartoma and Cowden syndrome. Patients with Cowden syndrome have an increased risk of developing epithelial thyroid cancer, follicular carcinoma being the most common, of up to 10% compared to <1% in the general population. The PTEN I101T has been observed in a variety of cancer types. One study identified the PTEN I101T variant in 1 out of 172 patients with germ line PTEN mutations. Of note, an in vitro studied observed that the PTEN I101T variant reduced the half-life of PTEN as well as significantly reduced its activity. Clinical trials using PI3K-beta inhibitor are available for patients with PTEN-deficient tumors.

Citations
  1. Yip L Molecular markers for thyroid cancer diagnosis, prognosis, and targeted therapy. J Surg Oncol 2015;111(1):43-50
  2. Xing M Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer 2013;13(3):184-99
  3. Gustafson S, et al. Cowden syndrome. Semin Oncol 2007;34(5):428-34
  4. Keniry M, et al. The role of PTEN signaling perturbations in cancer and in targeted therapy. Oncogene 2008;27(41):5477-85
  5. Landa I, et al. Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. J Clin Invest 2016;126(3):1052-66
  6. Wong CW, Or PMY, Wang Y, Li L, Li J, Yan M, Cao Y, Luk HM, Tong TMF, Leslie NR, Lo IF, Choy KW, Chan AML. Identification of a PTEN mutation with reduced protein stability, phosphatase activity, and nuclear localization in Hong Kong patients with autistic features, neurodevelopmental delays, and macrocephaly. Autism Res. 2018 Aug;11(8):1098-1109.
  7. Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S, Wilson CJ, Lehar J, Kryukov GV, Sonkin D, Reddy A, Liu M, Murray L, Berger MF, Monahan JE, Morais P, Meltzer J, Korejwa A, Jane-Valbuena J, Mapa FA, Thibault J, Bric-Furlong E, Raman P, Shipway A, Engels IH, Cheng J, Yu GK, Yu J, Aspesi P Jr, de Silva M, Jagtap K, Jones MD, Wang L, Hatton C, Palescandolo E, Gupta S, Mahan S, Sougnez C, Onofrio RC, Liefeld T, MacConaill L, Winckler W, Reich M, Li N, Mesirov JP, Gabriel SB, Getz G, Ardlie K, Chan V, Myer VE, Weber BL, Porter J, Warmuth M, Finan P, Harris JL, Meyerson M, Golub TR, Morrissey MP, Sellers WR, Schlegel R, Garraway LA. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012 Mar 28;483(7391):603-7.
  8. Pilarski R, Stephens JA, Noss R, Fisher JL, Prior TW. Predicting PTEN mutations: an evaluation of Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome clinical features. J Med Genet. 2011 Aug;48(8):505-12.
Last updated: 2019-01-22 18:29:19 UTC
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