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MTOR Gene Rearrangement

MedGen UID:
1665099
•Concept ID:
C4725936
•
Cell or Molecular Dysfunction
Synonyms: FK506 Binding Protein 12-Rapamycin Associated Protein 1 Gene Rearrangement; FRAP1 Gene Rearrangement; Mammalian Target of Rapamycin Gene Rearrangement; Mechanistic Target of Rapamycin Gene Rearrangement

Definition

A molecular abnormality indicating rearrangement of the MTOR gene. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMTOR Gene Rearrangement

Professional guidelines

PubMed

Molecularly Stratified Treatment Options in Primary Refractory DLBCL/HGBL with MYC and BCL2 or BCL6 Rearrangements (HGBL, NOS with MYC/BCL6).
Witte HM, Riedl J, Künstner A, Fähnrich A, Ketzer J, Fliedner SMJ, Reimer N, Bernard V, von Bubnoff N, Merz H, Busch H, Feller A, Gebauer N
Target Oncol 2023 Sep;18(5):749-765. Epub 2023 Jul 24 doi: 10.1007/s11523-023-00983-5. PMID: 37488307Free PMC Article
Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers: III: Molecular Pathology of Kidney Cancer.
Williamson SR, Gill AJ, Argani P, Chen YB, Egevad L, Kristiansen G, Grignon DJ, Hes O
Am J Surg Pathol 2020 Jul;44(7):e47-e65. doi: 10.1097/PAS.0000000000001476. PMID: 32251007Free PMC Article
Genotype directed therapy in murine mismatch repair deficient tumors.
Kucherlapati MH, Esfahani S, Habibollahi P, Wang J, Still ER, Bronson RT, Mahmood U, Kucherlapati RS
PLoS One 2013;8(7):e68817. Epub 2013 Jul 23 doi: 10.1371/journal.pone.0068817. PMID: 23935891Free PMC Article

Recent clinical studies

Etiology

Hybrid Capture-based Genomic Profiling of Circulating Tumor DNA From Patients With Advanced Ovarian Cancer.
Shen W, Shan B, Liang S, Zhang J, Yu Y, Zhang Y, Wang G, Bai Y, Qian B, Lu J, Jiang Z
Pathol Oncol Res 2021;27:581534. Epub 2021 Apr 9 doi: 10.3389/pore.2021.581534. PMID: 34257528Free PMC Article
Perivascular epithelioid cell tumors (PEComa) of the gynecologic tract.
Bennett JA, Oliva E
Genes Chromosomes Cancer 2021 Mar;60(3):168-179. Epub 2020 Nov 6 doi: 10.1002/gcc.22908. PMID: 33099813
Diverse Resistance Mechanisms to the Third-Generation ALK Inhibitor Lorlatinib in ALK-Rearranged Lung Cancer.
Recondo G, Mezquita L, Facchinetti F, Planchard D, Gazzah A, Bigot L, Rizvi AZ, Frias RL, Thiery JP, Scoazec JY, Sourisseau T, Howarth K, Deas O, Samofalova D, Galissant J, Tesson P, Braye F, Naltet C, Lavaud P, Mahjoubi L, Abou Lovergne A, Vassal G, Bahleda R, Hollebecque A, Nicotra C, Ngo-Camus M, Michiels S, Lacroix L, Richon C, Auger N, De Baere T, Tselikas L, Solary E, Angevin E, Eggermont AM, Andre F, Massard C, Olaussen KA, Soria JC, Besse B, Friboulet L
Clin Cancer Res 2020 Jan 1;26(1):242-255. Epub 2019 Oct 4 doi: 10.1158/1078-0432.CCR-19-1104. PMID: 31585938Free PMC Article
Large-scale assessment of the gliomasphere model system.
Laks DR, Crisman TJ, Shih MY, Mottahedeh J, Gao F, Sperry J, Garrett MC, Yong WH, Cloughesy TF, Liau LM, Lai A, Coppola G, Kornblum HI
Neuro Oncol 2016 Oct;18(10):1367-78. Epub 2016 Apr 25 doi: 10.1093/neuonc/now045. PMID: 27116978Free PMC Article
Aberrant STAT5 and PI3K/mTOR pathway signaling occurs in human CRLF2-rearranged B-precursor acute lymphoblastic leukemia.
Tasian SK, Doral MY, Borowitz MJ, Wood BL, Chen IM, Harvey RC, Gastier-Foster JM, Willman CL, Hunger SP, Mullighan CG, Loh ML
Blood 2012 Jul 26;120(4):833-42. Epub 2012 Jun 8 doi: 10.1182/blood-2011-12-389932. PMID: 22685175Free PMC Article

Diagnosis

Perivascular epithelioid cell tumors (PEComa) of the gynecologic tract.
Bennett JA, Oliva E
Genes Chromosomes Cancer 2021 Mar;60(3):168-179. Epub 2020 Nov 6 doi: 10.1002/gcc.22908. PMID: 33099813
Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers: III: Molecular Pathology of Kidney Cancer.
Williamson SR, Gill AJ, Argani P, Chen YB, Egevad L, Kristiansen G, Grignon DJ, Hes O
Am J Surg Pathol 2020 Jul;44(7):e47-e65. doi: 10.1097/PAS.0000000000001476. PMID: 32251007Free PMC Article
Characterization of genomic alterations and the significance of PI3K/mTOR pathway mutations and tumor mutational burden in non‑small cell lung cancer.
Hu J, Shang Y, Shi X, Zhang S, Shi J, Yao M, Wang A, Shou T, Shi W, Wang K, Liu A, Pan X, Wang Y
Oncol Rep 2020 Jun;43(6):2053-2061. Epub 2020 Mar 23 doi: 10.3892/or.2020.7559. PMID: 32236597
Diverse Resistance Mechanisms to the Third-Generation ALK Inhibitor Lorlatinib in ALK-Rearranged Lung Cancer.
Recondo G, Mezquita L, Facchinetti F, Planchard D, Gazzah A, Bigot L, Rizvi AZ, Frias RL, Thiery JP, Scoazec JY, Sourisseau T, Howarth K, Deas O, Samofalova D, Galissant J, Tesson P, Braye F, Naltet C, Lavaud P, Mahjoubi L, Abou Lovergne A, Vassal G, Bahleda R, Hollebecque A, Nicotra C, Ngo-Camus M, Michiels S, Lacroix L, Richon C, Auger N, De Baere T, Tselikas L, Solary E, Angevin E, Eggermont AM, Andre F, Massard C, Olaussen KA, Soria JC, Besse B, Friboulet L
Clin Cancer Res 2020 Jan 1;26(1):242-255. Epub 2019 Oct 4 doi: 10.1158/1078-0432.CCR-19-1104. PMID: 31585938Free PMC Article
Dual PI3K/mTOR inhibition shows antileukemic activity in MLL-rearranged acute myeloid leukemia.
Sandhöfer N, Metzeler KH, Rothenberg M, Herold T, Tiedt S, Groiß V, Carlet M, Walter G, Hinrichsen T, Wachter O, Grunert M, Schneider S, Subklewe M, Dufour A, Fröhling S, Klein HG, Hiddemann W, Jeremias I, Spiekermann K
Leukemia 2015 Apr;29(4):828-38. Epub 2014 Oct 17 doi: 10.1038/leu.2014.305. PMID: 25322685

Therapy

Discovery and functional characterization of the oncogenicity and targetability of a novel NOTCH1-ROS1 gene fusion in pediatric angiosarcoma.
Jain P, Iyer S, Straka J, Surrey LF, Pogoriler J, Han H, Smith T, Busch C, Fox E, Li M, Waanders AJ, Resnick A, Davare MA
Cold Spring Harb Mol Case Stud 2022 Oct;8(6) Epub 2022 Oct 28 doi: 10.1101/mcs.a006222. PMID: 36307212Free PMC Article
Diverse Resistance Mechanisms to the Third-Generation ALK Inhibitor Lorlatinib in ALK-Rearranged Lung Cancer.
Recondo G, Mezquita L, Facchinetti F, Planchard D, Gazzah A, Bigot L, Rizvi AZ, Frias RL, Thiery JP, Scoazec JY, Sourisseau T, Howarth K, Deas O, Samofalova D, Galissant J, Tesson P, Braye F, Naltet C, Lavaud P, Mahjoubi L, Abou Lovergne A, Vassal G, Bahleda R, Hollebecque A, Nicotra C, Ngo-Camus M, Michiels S, Lacroix L, Richon C, Auger N, De Baere T, Tselikas L, Solary E, Angevin E, Eggermont AM, Andre F, Massard C, Olaussen KA, Soria JC, Besse B, Friboulet L
Clin Cancer Res 2020 Jan 1;26(1):242-255. Epub 2019 Oct 4 doi: 10.1158/1078-0432.CCR-19-1104. PMID: 31585938Free PMC Article
Multiple gene aberrations and breast cancer: lessons from super-responders.
Wheler JJ, Atkins JT, Janku F, Moulder SL, Yelensky R, Stephens PJ, Kurzrock R
BMC Cancer 2015 May 29;15:442. doi: 10.1186/s12885-015-1439-y. PMID: 26021831Free PMC Article
Genotype directed therapy in murine mismatch repair deficient tumors.
Kucherlapati MH, Esfahani S, Habibollahi P, Wang J, Still ER, Bronson RT, Mahmood U, Kucherlapati RS
PLoS One 2013;8(7):e68817. Epub 2013 Jul 23 doi: 10.1371/journal.pone.0068817. PMID: 23935891Free PMC Article
The evolution of the TOR pathway and its role in cancer.
Beauchamp EM, Platanias LC
Oncogene 2013 Aug 22;32(34):3923-32. Epub 2012 Dec 17 doi: 10.1038/onc.2012.567. PMID: 23246968

Prognosis

Aggressive B-cell Lymphoma with MYC/TP53 Dual Alterations Displays Distinct Clinicopathobiological Features and Response to Novel Targeted Agents.
Deng M, Xu-Monette ZY, Pham LV, Wang X, Tzankov A, Fang X, Zhu F, Visco C, Bhagat G, Dybkaer K, Chiu A, Tam W, Zu Y, Hsi ED, You H, Huh J, Ponzoni M, Ferreri AJM, Møller MB, Parsons BM, Hagemeister F, van Krieken JH, Piris MA, Winter JN, Li Y, Xu B, Liu P, Young KH
Mol Cancer Res 2021 Feb;19(2):249-260. Epub 2020 Nov 5 doi: 10.1158/1541-7786.MCR-20-0466. PMID: 33154093Free PMC Article
Perivascular epithelioid cell tumors (PEComa) of the gynecologic tract.
Bennett JA, Oliva E
Genes Chromosomes Cancer 2021 Mar;60(3):168-179. Epub 2020 Nov 6 doi: 10.1002/gcc.22908. PMID: 33099813
Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers: III: Molecular Pathology of Kidney Cancer.
Williamson SR, Gill AJ, Argani P, Chen YB, Egevad L, Kristiansen G, Grignon DJ, Hes O
Am J Surg Pathol 2020 Jul;44(7):e47-e65. doi: 10.1097/PAS.0000000000001476. PMID: 32251007Free PMC Article
Potential Resistance Mechanisms Revealed by Targeted Sequencing from Lung Adenocarcinoma Patients with Primary Resistance to Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs).
Zhong J, Li L, Wang Z, Bai H, Gai F, Duan J, Zhao J, Zhuo M, Wang Y, Wang S, Zang W, Wu M, An T, Rao G, Zhu G, Wang J
J Thorac Oncol 2017 Dec;12(12):1766-1778. Epub 2017 Aug 14 doi: 10.1016/j.jtho.2017.07.032. PMID: 28818608
Genomic dissection of Hurthle cell carcinoma reveals a unique class of thyroid malignancy.
Ganly I, Ricarte Filho J, Eng S, Ghossein R, Morris LG, Liang Y, Socci N, Kannan K, Mo Q, Fagin JA, Chan TA
J Clin Endocrinol Metab 2013 May;98(5):E962-72. Epub 2013 Mar 29 doi: 10.1210/jc.2012-3539. PMID: 23543667Free PMC Article

Clinical prediction guides

Perivascular epithelioid cell tumors (PEComa) of the gynecologic tract.
Bennett JA, Oliva E
Genes Chromosomes Cancer 2021 Mar;60(3):168-179. Epub 2020 Nov 6 doi: 10.1002/gcc.22908. PMID: 33099813
Characterization of genomic alterations and the significance of PI3K/mTOR pathway mutations and tumor mutational burden in non‑small cell lung cancer.
Hu J, Shang Y, Shi X, Zhang S, Shi J, Yao M, Wang A, Shou T, Shi W, Wang K, Liu A, Pan X, Wang Y
Oncol Rep 2020 Jun;43(6):2053-2061. Epub 2020 Mar 23 doi: 10.3892/or.2020.7559. PMID: 32236597
Multiple gene aberrations and breast cancer: lessons from super-responders.
Wheler JJ, Atkins JT, Janku F, Moulder SL, Yelensky R, Stephens PJ, Kurzrock R
BMC Cancer 2015 May 29;15:442. doi: 10.1186/s12885-015-1439-y. PMID: 26021831Free PMC Article
Dual PI3K/mTOR inhibition shows antileukemic activity in MLL-rearranged acute myeloid leukemia.
Sandhöfer N, Metzeler KH, Rothenberg M, Herold T, Tiedt S, Groiß V, Carlet M, Walter G, Hinrichsen T, Wachter O, Grunert M, Schneider S, Subklewe M, Dufour A, Fröhling S, Klein HG, Hiddemann W, Jeremias I, Spiekermann K
Leukemia 2015 Apr;29(4):828-38. Epub 2014 Oct 17 doi: 10.1038/leu.2014.305. PMID: 25322685
Aberrant STAT5 and PI3K/mTOR pathway signaling occurs in human CRLF2-rearranged B-precursor acute lymphoblastic leukemia.
Tasian SK, Doral MY, Borowitz MJ, Wood BL, Chen IM, Harvey RC, Gastier-Foster JM, Willman CL, Hunger SP, Mullighan CG, Loh ML
Blood 2012 Jul 26;120(4):833-42. Epub 2012 Jun 8 doi: 10.1182/blood-2011-12-389932. PMID: 22685175Free PMC Article

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