REVIEW PAPER
PTEN gene mutations in malignant tumours – a systematic review and clinical implications for tumour treatment
1
Collegium Medicum, Jan Kochanowski University, Kielce, Poland Head of the Collegium: Prof. Marianna Janion MD PhD
2
Kielce Province Cancer Centre, Kielce, Poland Head of the Centre: Prof. Stanisław Góźdż MD, PhD
3
Institute of Physics, Jan Kochanowski University, Kielce, Poland Head of the Institute: Prof. Marek Pajek
Submission date: 2022-08-01
Final revision date: 2022-10-23
Acceptance date: 2022-11-13
Publication date: 2022-12-16
Medical Studies 2022;38(4):336-350
KEYWORDS
TOPICS
ABSTRACT
Introduction:
The PTEN (phosphatase and tensin homologue deleted on chromosome 10) gene is one of the most commonly mutated suppressor genes in malignant tumours. PTEN protein counteracts the process of carcinogenesis by inhibition of many kinases promoting cell proliferation.
Aim of the research:
A review and analysis of detected PTEN gene mutations in malignant tumours and identification of the most commonly mutated sites in the PTEN gene.
Material and methods:
The systematic review included 70 publications.
Results:
Mutations in the PTEN gene were found in 18% of cases. The largest number of mutations were observed in endometrial cancer – 49% of examined patients. Mutations most frequently occurred in exon 5 (49% of examined cases), followed by exon 8 (15% of cases) and exon 7 (13% of cases).
Conclusions:
The identification of mutations in the PTEN gene in malignant tumours is of great clinical importance – targeted treatment with temsirolimus and everolimus is available for patients.
The PTEN (phosphatase and tensin homologue deleted on chromosome 10) gene is one of the most commonly mutated suppressor genes in malignant tumours. PTEN protein counteracts the process of carcinogenesis by inhibition of many kinases promoting cell proliferation.
Aim of the research:
A review and analysis of detected PTEN gene mutations in malignant tumours and identification of the most commonly mutated sites in the PTEN gene.
Material and methods:
The systematic review included 70 publications.
Results:
Mutations in the PTEN gene were found in 18% of cases. The largest number of mutations were observed in endometrial cancer – 49% of examined patients. Mutations most frequently occurred in exon 5 (49% of examined cases), followed by exon 8 (15% of cases) and exon 7 (13% of cases).
Conclusions:
The identification of mutations in the PTEN gene in malignant tumours is of great clinical importance – targeted treatment with temsirolimus and everolimus is available for patients.
REFERENCES (85)
1.
Kechagioglou P, Papi RM, Provatopoulou X, Kalogera E, Papadimitriou E, Grigoropoulos P, Nonni A, Zogra- fos G, Kyriakidis DA, Gounaris A. Tumor suppressor PTEN in breast cancer: heterozygosity, mutations and protein expression. Anticancer Res 2014; 34: 1387-1400.
2.
Krześlak A. Kinaza Akt: kluczowy regulator metabolizmu i progresji nowotworów [Akt kinase: a key regulator of metabolism and progression of tumors]. Postepy Hig Med Dosw 2010; 64: 490-503.
3.
Gkountakos A, Sartori G, Falcone I, Piro G, Ciuffreda L, Carbone C, Tortora G, Scarpa A, Bria E, Milella M, Ro- sell R, Corbo V,*Pilotto S. PTEN in lung cancer: dealing with the problem, building on new knowledge and turning the game around. Cancers 2019; 11: 1141.
4.
Pópulo H, Lopes JM, Soares P. The mTOR signalling pathway in human cancer. Int J Mol Sci 2012; 13: 1886-1918.
5.
Phin S, Moore MW, Cotter PD. Genomic rearrangements of PTEN in prostate cancer. Front Oncol 2013; 3: 240.
6.
Krawczyk B, Rychlewski P, Fabianowska-Majewska K. PTEN – tumor suppressor protein: regulation of protein activity and gene expression. Post Biol Kom 2006; 33: 365-380.
7.
Chen CY, Chen J, He L, Stiles BL. PTEN: tumor suppressor and metabolic regulator. Front Endocrinol 2018; 9: 338.
8.
Saito Y, Gopalan B, Mhashilkar AM, Roth JA, Chada S, Zumstein L, Ramesh R. Adenovirus-mediated PTEN treatment combined with caffeine produces a synergistic therapeutic effect in colorectal cancer cells. Cancer Gene Ther 2003; 10: 803-813.
9.
Dempsey DR, Cole PA. Protein chemical approaches to understanding PTEN lipid phosphatase regulation. Meth Enzymol 2018; 607: 405-422.
10.
Aguissa-Touré AH, Li G. Genetic alterations of PTEN in human melanoma. Cell Mol Life Sci 2012; 69: 1475-1491.
11.
Rahdar M, Inoue T, Meyer T, Zhang J, Vazquez F, Devreotes PN. A phosphorylation-dependent intramolecular interaction regulates the membrane association and activity of the tumor suppressor PTEN. Proc Natl Acad Sci USA 2009; 106: 480-485.
12.
. Li XH, Zheng HC, Takahashi H, Masuda S, Yang XH, Takano Y. PTEN expression and mutation in colorectal carcinomas. Oncol Rep 2009; 22: 757-764.
13.
Morisaki T, Kashiwagi S, Kouhashi R, Yabumoto A, Asa- no Y, Takashima T, Hirakawa K, Ohira M. Cowden syndrome diagnosed by bilateral breast cancer with lhermitte-duclos disease: a case report. Case Rep Oncol 2020; 13: 419-423.
14.
Goral V. Pancreatic cancer: pathogenesis and diagnosis. Asian Pac J Cancer Prev 2015; 16: 5619-5624.
15.
Chu EC, Tarnawski AS. PTEN regulatory functions in tumor suppression and cell biology. Med Sci Monit 2004; 10: RA235-RA241.
16.
Naguib A, Trotman LC. PTEN plasticity: how the taming of a lethal gene can go too far. Trends Cell Biol 2013; 23: 374-379.
17.
Datta N, Chakraborty S, Basu M, Ghosh MK. Tumor suppressors having oncogenic functions: the double agents. Cells 2020; 10: 46.
18.
Uemura S, Matsubayashi H, Kiyozumi Y, Uesaka K, Yamamoto Y, Sasaki K, Abe M, Urakami K, Kusuhara M, Yamaguchi K; Pancreatic adenocarcinoma with a germline PTEN p.Arg234Gln mutation. Familial cancer. 2018; 17: 255-259.
19.
Young G, Wang K, He J, Otto G, Hawryluk M, Zwirco Z, Brennan T, Nahas M, Donahue A, Yelensky R, Lipson D, Sheehan CE, Boguniewicz AB, Stephens PJ, Miller VA, Ross JS. Clinical next-generation sequencing successfully applied to fine-needle aspirations of pulmonary and pancreatic neoplasms. Cancer Cytopathol 2013; 121: 688-694.
20.
Feilotter HE, Coulon V, McVeigh JL, Boag AH, Dorion-Bonnet F, Duboué B, Latham WC, Eng C, Mulligan LM, Longy M Analysis of the 10q23 chromosomal region and the PTEN gene in human sporadic breast carcinoma. Br J Cancer 1999; 79: 718-723.
21.
Liang X, Briaux A, Becette V, Benoist C, Boulai A, Chemlali W, Schnitzler A, Baulande S, Rivera S, Mouret-Rey- nier MA, Bouvet LV, De La Motte Rouge T, Lemonnier J, Lerebours F, Callens C. Molecular profiling of hormone receptor-positive, HER2-negative breast cancers from patients treated with neoadjuvant endocrine therapy in the CARMINA 02 trial (UCBG-0609). J Hematol Oncol 2018; 11: 124.
22.
Li G, Guo X, Chen M, Tang L, Jiang H, Day JX, Xie Y, Peng L, Xu X, Li J, Wang S, Xiao Z, Dai L, Wang J. Prevalence and spectrum of AKT1, PIK3CA, PTEN and TP53 somatic mutations in Chinese breast cancer patients. PLoS One 2018; 13: e0203495.
23.
Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, Ne- ve RM, Kuo WL, Davies M, Carey M, Hu Z, Guan Y, Sa- hin A, Fraser Symmans W, Pusztai L, Nolden LK, Horlings H, Berns K, Hung MC, van de Vijver MJ, Valero V, Gray JW, Bernards R, Mills GB, Hennessy BT. An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res 2008; 68: 6084-6091.
24.
Mitus J, Adamczyk A, Majchrzyk K, Kowalik A, Ryś J, Niemiec J. Comparison of mutation profile between primary phyllodes tumors of the breast and their paired local recurrences. Pol J Pathol 2020; 71: 7-12.
25.
Tang MHE, Dahlgren M, Brueffer C, Tjitrowirjo T, Winter C, Chen Y, Olsson E, Wang K, Törngren T, Sjöström M, Grabau D, Bendahl PO, Rydén L, Niméus E, Saal LH, Borg Å, Gruvberger-Saal SK. Remarkable similarities of chromosomal rearrangements between primary human breast cancers and matched distant metastases as revealed by whole-genome sequencing. Oncotarget 2015; 6: 37169-3784.
26.
Kmak JA, Agarwal N, He Y, Heilmann AM, Miller VA, Ross JS, Pal SK, Ali SM, Kilari D. Exceptional response to everolimus in a patient with metastatic castrate-resistant prostate cancer harboring a PTEN inactivating mutation. Case Rep Oncol 2020; 13: 456-4461.
27.
Julka PK, Verma A, Gupta K. Personalized treatment approach to metastatic castration-resistant prostate cancer with BRCA2 and PTEN mutations: a case report. Case Rep Oncol 2020; 13: 55-61.
28.
Wilkinson S, Harmon SA, Terrigino NT, Karzai F, Pin- to PA, Madan RA, VanderWeele DJ, Lake R, Atway R, Bright JR, Carrabba NV, Trostel SY, Lis RT, Chun G, Gul- ley JL, Merino MJ, Choyke PL, Ye H, Dahut WL, Turk- bey B, Sowalsky AG. A case report of multiple primary prostate tumors with differential drug sensitivity. Nat Commun 2020; 11: 837.
29.
Haffner MC, Mosbruger T, Esopi DM, Fedor H, Hea- phy CM, Walker DA, Adejola N, Gürel M, Hicks J, Meeker AK, Halushka MK, Simons JW, Isaacs WB, De Marzo A, Nelson WG, Yegnasubramanian S. Tracking the clonal origin of lethal prostate cancer. J Clin Invest 2013; 123: 4918-4922.
30.
Hussain M, Daignault-Newton S, Twardowski PW, Albany C, Stein MN, Kunju LP, Siddiqui J, Wu YM, Robinson D, Lonigro RJ, Cao X, Tomlins SA, Mehra R, Coo- ney KA, Montgomery B, Antonarakis ES, Shevrin DH, Corn PG, Whang YE, Smith DC, Caram MV, Knu- dsen KE, Stadler WM, Feng FY, Chinnaiyan AM. Targeting androgen receptor and DNA repair in metastatic castration-resistant prostate cancer: results from NCI 9012. J Clin Oncol 2018; 36: 991-999.
31.
Uruga H, Fujii T, Nakamura N, Moriguchi S, Kishi K, Takaya H. Squamous cell transformation as a mechanism of acquired resistance to tyrosine kinase inhibitor in EGFR-mutated lung adenocarcinoma: a report of two cases. Respirol Case Rep 2020; 8: e00521.
32.
Wang L, Dong F, Su J, Du G, Shao Y, Liu Y, He X, Bao L, Wang W, Guo X, Wang X. Resistance to both chemotherapy and EGFR-TKI in small cell lung cancer with EGFR 19-Del mutation: a case report. Front Oncol 2020; 10: 1048.
33.
Parikh AR, Ali SM, Schrock AB, Albacker LA, Miller VA, Stephens PJ, Crilley P, Markman M. Response to rapamycin analogs but not PD-1 inhibitors in PTEN-mutated metastatic non-small-cell lung cancer with high tumor mutational burden. Lung Cancer 2018; 9: 45-47.
34.
Hayashi T, Takamochi K, Yanai Y, Mitani K, Tomita H, Mogushi K, Suehara Y, Takahashi F, Suzuki K, Saito T, Yao T. Non-small cell lung carcinoma with diffuse coexpression of thyroid transcription factor-1 and Np63/p40. Human Pathol 2018; 78: 177-181.
35.
Miyoshi T, Umemura S, Matsumura Y, Mimaki S, Tada S, Makinoshima H, Ishii G, Udagawa H, Matsumoto S, Yoh K, Niho S, Ohmatsu H, Aokage K, Hishida T, Yoshi- da J, Nagai K, Goto K, Tsuboi M, Tsuchihara K. Genomic profiling of large-cell neuroendocrine carcinoma of the lung. Clin Cancer Res 2017; 23: 757-765.
36.
Akizuki K, Sekine M, Kogure Y, Kameda T, Shide K, Koya J, Kamiunten A, Kubuki Y, Tahira Y, Hidaka T, Kiwaki T, Tanaka H, Sato Y, Kataoka H, Kataoka K, Shimo- da K. TP53 and PTEN mutations were shared in concurrent germ cell tumor and acute megakaryoblastic leukemia. BMC Cancer 2020; 20: 5.
37.
Matsubayashi H, Higashigawa S, Kiyozumi Y, Horiuchi Y, Hirashima Y, Kado N, et al. Abe M, Takuma O, Sumiko O, Kenichi U, Ken Y. Metachronous ovarian endometrioid carcinomas in a patient with a PTEN variant: case report of incidentally detected Cowden syndrome. BMC Cancer 2019; 19: 1014.
38.
Li W, Di Shao, Li L, Wu M, Ma S, Tan X, Zhong S, Guo F, Wang Z, Ye M. Germline and somatic mutations of multi-gene panel in Chinese patients with epithelial ovarian cancer: a prospective cohort study. J Ovarian Res 2019; 12: 80.
39.
Yauy K, Imbert-Bouteille M, Bubien V, Lindet-Bour- geois C, Rathat G, Perrochia H, MacGrogan G, Longy M, Bessis D, Tinat J, Baert-Desurmont S, Blanluet M, Per- re PV, Baudry K, Pujol P, Corsini C. Ovarian clear cell carcinoma in Cowden syndrome. J Natl Compr Canc Netw 2019; 17: 7-11.
40.
McConechy MK, Ding J, Senz J, Yang W, Melnyk N, To- ne AA, Prentice LM, Wiegand KC, McAlpine JN, Shah SP, Lee CH, Goodfellow PJ, Gilks CB, Huntsman DG. Ovarian and endometrial endometrioid carcinomas have distinct CTNNB1 and PTEN mutation profiles. Mod Pathol 2014; 27: 128-134.
41.
Fu S, Hennessy BT, Ng CS, Ju Z, Coombes KR, Wolf JK, Sood AK, Levenback CF, Coleman RL, Kavanagh JJ, Gershenson DM, Markman M, Dice K, Howard A, Li J, Li Y, Stemke-Hale K, Dyer M, Atkinson E, Jackson E, Kundra V, Kurzrock R, Bast Jr RC, Mills GB. Perifosine plus docetaxel in patients with platinum and taxane resistant or refractory high-grade epithelial ovarian cancer. Gynecol Oncol 2012; 126: 47-53.
42.
Kuo KT, Mao TL, Jones S, Veras E, Ayhan A, Wang TL, Glas R, Slamon D, Velculescu VE, Kuman RJ, Shih IM. Frequent activating mutations of PIK3CA in ovarian clear cell carcinoma. Am J Pathol 2009; 174: 1597-1601.
43.
Elvin JA, Chura J, Gay LM, Markman M. Comprehensive genomic profiling (CGP) of ovarian clear cell carcinomas (OCCC) identifies clinically relevant genomic alterations (CRGA) and targeted therapy options. Gynecol Oncol Rep 2017; 20: 62-66.
44.
Wang M, Fan W, Ye M, Tian C, Zhao L, Wang J, Han W, Yang W, Gu C, Li M, Zhang Z, Wang Y, Zhang H, Meng Y. Molecular profiles and tumor mutational burden analysis in Chinese patients with gynecologic cancers. Sci Rep 2018; 8: 8990.
45.
Sui M, Li Y, Wang H, Luo Y, Wan T, Wang X, Hu B, Cheng Y, Lv X, Xin X, Xu Q, Wang G, Lu S. Two cases of intrahepatic cholangiocellular carcinoma with high insertion-deletion ratios that achieved a complete response following chemotherapy combined with PD-1 blockade. J Immunother Cancer 2019; 7: 125.
46.
Villanueva A, Chiang DY, Newell P, Peix J, Thung S, Alsinet C, Tovar V, Roayaie S, Minguez B, Sole M, Batti- ston C, Van Laarhoven S, Fiel MI, Di Feo A, Hoshida Y, Yea S, Toffanin S, Ramos A, Martignetti JA, Mazzafer- ro V, Bruix J, Waxman S, Schwartz M, Meyerson M, Friedman SL, Llovet JM. Pivotal role of mTOR signaling in hepatocellular carcinoma. Gastroenterology 2008; 135: 1972-1983.
47.
Kuno I, Yoshida H, Kohno T, Ochiai A, Kato T. Endometrial cancer arising after complete remission of uterine malignant lymphoma: A case report and mutation analysis. Gynecol Oncol Rep. 2019; 28: 50-53.
48.
Martignetti JA, Pandya D, Nagarsheth N, Chen Y, Camacho O, Tomita S, Brodman M, Ascher-Walsh C, Kolev V, Cohen S, Harkins TT, Schadt EE, Reva B, Sebra R, Dotti- no P. Detection of endometrial precancer by a targeted gynecologic cancer liquid biopsy. Cold Spring Harb Mol Case Stud 2018; 4: a003269.
49.
Matsuura M, Yamaguchi K, Tamate M, Satohisa S, Teramoto M, Iwasaki M, Sugita S, Hasegawa T, Koubo R, Takane K, Ikenoue T, Furukawa Y, Saito T. Efficacy of liquid- based genetic diagnosis of endometrial cancer. Cancer Sci 2018; 109: 4025-4032.
50.
Oza AM, Elit L, Tsao MS, Kamel-Reid S, Biagi J, Provencher DM, Gotlieb WH, Hoskins PJ, Ghatage P, Tonkin KS, Mackay HJ, Mazurka J, Sederias J, Ivy P, Dancey JE, Eisenhauer EA. Phase II study of temsirolimus in women with recurrent or metastatic endometrial cancer: a trial of the NCIC Clinical Trials Group. J Clin Oncol 2011; 29: 3278-3285.
51.
Kafshdooz L, Kafshdooz T, Tabrizi AD, Mohaddes Arda- bili SM, Akbarzadeh A, Gharesouran J, Ghojazadeh M, Farajnia S. Role of exon 7 PTEN gene in endometrial carcinoma. Asian Pac J Cancer Prev 2015; 16: 4521-4524.
52.
Djordjevic B, Hennessy BT, Li J, Barkoh BA, Luthra R, Mills GB, Broaddus RR. Clinical assessment of PTEN loss in endometrial carcinoma: immunohistochemistry outperforms gene sequencing. Mod Pathol 2012; 25: 699-708.
53.
Polymeros K, Guttery DS, Hew R, Bishop R, Stannard E, Macip S, Symonds P, Moss EL. Differences in the molecular profile of endometrial cancers from British White and British South Asian women. PLoS One 2020; 15: e0233900.
54.
Kogan L, Octeau D, Amajoud Z, Abitbol J, Laskov I, Ferenczy A, Pelmus M, Eisenberg N, Kessous R, Lau S, Yasmeen A, Gotlieb WH, Salvador S. Impact of lower uterine segment involvement in type II endometrial cancer and the unique mutational profile of serous tumors. Gynecol Oncol Rep 2018; 24: 43-47.
55.
Bendell JC, Varghese AM, Hyman DM, Bauer TM, Pant S, Callies S, Lin J, Martinez R, Wickremsinhe E, Fink A, Wacheck V, Moore KN. A first-in-human phase 1 study of LY3023414, an oral PI3K/mTOR dual inhibitor, in patients with advanced cancer. Clin Cancer Res 2018; 24: 3253-3262.
56.
Obata T, Nakamura M, Mizumoto Y, Matsumoto T, Takakura M, Fujiwara H. Synchronous endometrioid adenocarcinomas in the uterine cervix and corpus. J Obstet Gynaecol Res 2016; 42: 1390-1394.
57.
Ariura M, Kasajima R, Miyagi Y, Ishidera Y, Sugo Y, Oi Y, Hayashi H, Shigeta H, Miyagi E. Combined large cell neuroendocrine carcinoma and endometrioid carcinoma of the endometrium: a shared gene mutation signature between the two histological components. Int Cancer Conf J 2017; 6: 11-15.
58.
Sullivan SA, Hawkins G, Zhao X, Jo H, Hayes N, Deng X, Bandyopadhyay D, Bae-Jump VL, Rossi EC. Genomic profiling of endometrial cancer and relationship with volume of endometrial cancer disease spread. Gynecol Oncol Rep 2021; 36: 100720.
59.
Hembree TN, Teer JK, Hakam A, Chiappori AA. Genetic Investigation of uterine carcinosarcoma: case report and cohort analysis. Cancer Control 2016; 23: 61-66.
60.
Motaparthi K, George EV, Guo R. Distant metastasis due to heavily pigmented epithelioid melanoma with underlying BRAF V600E, NOTCH1, ERBB3, and PTEN mutations. J Cutan Pathol 2019; 46: 613-618.
61.
Zhou XP, Gimm O, Hampel H, Niemann T, Walker MJ, Eng C. Epigenetic PTEN Silencing in Malignant Melanomas without PTEN Mutation. Am J Pathol 2000; 157: 1123-1128.
62.
Agosto-Arroyo E, Rosa M, Chau A, Khazai L. Concurrent BRAF and PTEN mutations in melanoma of unknown origin presenting as a breast mass. SAGE Open Med Case Rep 2017; 5: 2050313X17711064.
63.
Galanina N, Kurzrock R. Successful implementation of genomically based treatment of chemotherapy refractory peripheral T-cell lymphoma (PTCL). Cancer Biol Ther 2019; 20: 247-251.
64.
Ishiguro K, Sasaki Y, Takagi Y, Niinuma T, Suzuki H, Tokino T, Hayashi T, Takahashi T, Igarashi T, Matsuno Y. Aggressive variant of splenic marginal zone lymphoma characterized using a cancer panel test and treated with rituximab-containing chemotherapy: a case report. Medicine 2020; 99: e21938.
65.
Trinquand A, Tanguy-Schmidt A, Ben Abdelali R, Lambert J, Beldjord K, Lengliné E, De Gunzburg N, Payet- Bornet D, Lhermitte L, Mossafa H, Lhéritier V, Bond J, Huguet F, Buzyn A, Leguay T, Cahn JY, Thomas X, Chalandon Y, Delannoy A, Bonmati C, Maury S, Nadel B, Macintyre E, Ifrah N, Dombret H, Asnafi V. Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study. J Clin Oncol 2013; 31: 4333-4342.
66.
Starr JS, Attia S, Joseph RW, Menke D, Casler J, Smallrid- ge RC. Follicular dendritic cell sarcoma presenting as a thyroid mass. J Clin Oncol. 2015; 33: e74-e76.
67.
Lin PC, Lin JK, Lin HH, Lan YT, Lin CC, Yang SH, Chen WS, Liang WY, Jiang JK, Chang SC. A comprehensive analysis of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) loss in colorectal cancer. World J Surg Oncol 2015; 13: 186.
68.
Peeters M, Oliner KS, Parker A, Siena S, van Cutsem E, Huang J, Humblet Y, Van Laethem JL, André T, Wiezo- rek J, Reese D, Patterson SD. Massively parallel tumor multigene sequencing to evaluate response to panitumumab in a randomized phase III study of metastatic colorectal cancer. Clin Cancer Res 2013; 19: 1902-1912.
69.
Byun DS, Cho K, Ryu BK, Lee MG, Park JI, Chae KS, Kim HJ, Chi SG. Frequent monoallelic deletion of PTEN and its reciprocal associatioin with PIK3CA amplification in gastric carcinoma. Int J Cancer2003; 104: 318-327.
70.
Werner D, Atmaca A, Pauligk C, Pustowka A, Jäger E, Al-Batran SE. Phase I study of everolimus and mitomycin C for patients with metastatic esophagogastric adenocarcinoma. Cancer Med 2013; 2: 325-333.
71.
Martin DR, LaBauve E, Pomo JM, Chiu VK, Hanson JA, Gullapalli RR. Site-specific genomic alterations in a well-differentiated pancreatic neuroendocrine tumor with high-grade progression. Pancreas 2018; 47: 502-510.
72.
Tate G, Suzuki T, Mitsuya T. Mutation of the PTEN gene in a human hepatic angiosarcoma. Cancer Genet Cytogenet 2007; 178: 160-162.
73.
Falbo V, Floridia G, Censi F, Marra M, Foschini MP, Taruscio D. Three cases of rare salivary gland tumours: a molecular study of TP53, CDKN2A/ARF, RAS, BRAF, PTEN, MAPK2 and EGFR genes. Oncol Rep 2011; 26: 3-11.
74.
Staal FJT, van der Luijt RB, Baert MRM, van Drunen J, van Bakel H, Peters E, de Valk I, van Amstel HKP, Tapho- orn MJB, Jansen GH, van Veelen CWM, Burgering B, Staal GEJ. A novel germline mutation of PTEN associated with brain tumours of multiple lineages. Br J Cancer 2002; 86: 1586-1591.
75.
Kraus JA, Glesmann N, Beck M, Krex D, Klockgether T, Schackert G, Schlegel U. Molecular analysis of the PTEN, TP53 and CDKN2A tumor suppressor genes in long-term survivors of glioblastoma multiforme. J Neurooncol 2000; 48: 89-94.
76.
Malmer B, Grönberg H, Andersson U, Jonsson BA, Henriksson R. Microsatellite instability, PTEN and p53 germline mutations in glioma families. Acta Oncol 2001; 40: 633-637.
77.
Reis RM, Herva R, Brandner S, Koivukangas J, Mironov N, Bär W, Kleihues P, Ohgaki H. Second primary glioblastoma. J Neuropathol Exp Neurol 2001; 60: 208-215.
78.
Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre PL, Burkhard C, Schüler D, Probst-Hensch NM, Maiorka PC, Baeza N Pisani P, Yonekawa Y, Yasargil MG, Lütolf, UM, Kleihues P. Genetic pathways to glioblastoma: a population-based study. Cancer Res 2004; 64: 6892-6899.
79.
Actor B, Cobbers JMJL, Büschges R, Wolter M, Knobbe CB, Lichter P, Reifenberger G, Weber RG. Comprehensive analysis of genomic alterations in gliosarcoma and its two tissue components. Genes Chromosomes Cancer 2002; 34: 416-427.
80.
Rasheed BK, Stenzel TT, McLendon RE, Parsons R, Friedman AH, Friedman HS, Bigner DD, Bigner SH. PTEN gene mutations are seen in high-grade but not in low-grade gliomas. Cancer Res 1997; 57: 4187-4190.
81.
Fukushima T, Favereaux A, Huang H, Shimizu T, Yonekawa Y, Nakazato Y, Ohagki H. Genetic alterations in primary glioblastomas in Japan. J Neuropathol Exp Neurol 2006; 65: 12-18.
82.
Li G, Zhang Z, Zhang J, Jin T, Liang H, Gong L, Cui G, Yang H, He S, Zhang Y, Gao G. Occipital anaplastic oligodendroglioma with multiple organ metastases after a short clinical course: a case report and literature review. Diagn Pathol 2014; 9: 17.
83.
Broniscer A, Baker SJ, Stewart CF, Merchant TE, Laningham FH, Schaiquevich P, Kocak M, Morris EB, Ender- sby R, Ellison DW, Gajjar A. Phase I and pharmacokinetic studies of erlotinib administered concurrently with radiotherapy for children, adolescents, and young adults with high-grade glioma. Clin Cancer Res 2009; 15: 701-707.
84.
Ansari D, Tingstedt B, Andersson B, Holmquist F, Sturesson C, Williamsson C, Sasor A, Borg D, Bauden M, Andersson R. Pancreatic cancer: yesterday, today and tomorrow. Future Oncol 2016; 12: 1929-1946.
85.
Hocking C, Hardingham JE, Broadbridge V, Wrin J, Townsend AR, Tebbutt N, Cooper J, Ruszkiewicz A, Lee C Price TJ. Can we accurately report PTEN status in advanced colorectal cancer? BMC Cancer 2014; 14: 128.
| eISSN: | 2300-6722 |
| ISSN: | 1899-1874 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
