Interactions: In mice, the FIG-ROS1 fusion gene has been shown to promote the formation of astrocytomas when ectopically expressed in the basal ganglia, and the EZR-ROS1 fusion gene has been shown to promote lung adenocarcinoma when ectopically expressed in lung epithelium
Yoshida A, Tsuta K, Wakai S, Arai Y, Asamura H, Shibata T, Furuta K, Kohno T, Kushima R. Immunohistochemical detection of ROS1 is useful for identifying ROS1 rearrangements in lung cancers / Mod Pathol, v.27, issue 5, November, 2014, pp.711-20
Sentences: CD74-ROS1 and EZR-ROS1 fusions were significantly associated with at least focal globular immunoreactivity and plasma membranous accentuation, respectively, and these patterns were specific to ROS1-rearranged cases.
Li H, Pan Y, Wang R, Li Y, Sun Y, Chen H. Response to crizotinib observed in metastatic mediastinum lymph node from a non-small cell lung cancer patient harboring EZR–ROS1 fusion / J Cancer Res Clin Oncol., v.141, issue 1, January, 2015, pp.185-7
Sentences: To the best of our knowledge, this is the first report about NSCLC patient with EZR–ROS1 fusion gene type responding to crizotinib.
Inoue M, Toki H, Matsui J, Togashi Y, Dobashi A, Fukumura R, Gondo Y, Minowa O, Tanaka N, Mori S, Takeuchi K, Noda T. Mouse models for ROS1-fusion-positive lung cancers and their application to the analysis of multikinase inhibitor efficiency / Carcinogenesis, v.37, issue 5, May, 2016, pp.452-60
Sentences: Although at least 12 partner genes for ROS1 have been identified in human NSCLCs so far, only one TG mouse lung cancer model (EZR-ROS1 TG mouse) has been established
Davare MA, Davare MA, Davare MA, Davare MA, Davare MA, Saborowski A, Saborowski A, Saborowski A, Saborowski A, Saborowski A, Eide CA, Eide CA, Eide CA, Eide CA, Eide CA, Tognon C, Tognon C, Tognon C, Tognon C, Tognon C, Smith RL, Smith RL, Smith RL, Smith RL, Smith RL, Elferich J, Elferich J, Elferich J, Elferich J, Elferich J, Agarwal A, Agarwal A, Agarwal A, Agarwal A, Agarwal A, Tyner JW, Tyner JW, Tyner JW, Tyner JW, Tyner JW, Shinde UP, Shinde UP, Shinde UP, Shinde UP, Shinde UP, Lowe SW, Lowe SW, Lowe SW, Lowe SW, Lowe SW, Druker BJ, Druker BJ, Druker BJ, Druker BJ, Druker BJ. Foretinib is a potent inhibitor of oncogenic ROS1 fusion proteins / Proc Natl Acad Sci U S A., v.110, issue 48, November, 2013, pp.196519-24
Sentences: Other ROS1 fusions include CD74–ROS1, EZR–ROS1, LRIG3–ROS1, SDC4–ROS1, and TPM3–ROS1
Arai Y, Totoki Y, Takahashi H, Nakamura H, Hama N, Kohno T, Tsuta K, Yoshida A, Asamura H, Mutoh M, Hosoda F, Tsuda H, Shibata T. Mouse Model for ROS1-Rearranged Lung Cancer / PLoS One, v.8, issue 2, February, 2013, pp.e56010
Sentences: The present study shows that EZR-ROS1 plays an essential role in the oncogenesis of NSCLC harboring the fusion gene.
Solomon B. Validating ROS1 Rearrangements As a Therapeutic Target in Non–Small-Cell Lung Cancer / J Clin Oncol., v.33, issue 9, March, 2015, pp.972-4
Sentences: At least 11 fusion partners have been identified in NSCLC, including CD74-ROS1, SDC4-ROS1, EZR-ROS1, and SLC34A2-ROS1, all of which maintain a constant breakpoint in ROS1, preserving the kinase domain and resulting in aberrant ROS1 expression with constitutive kinase activity.
Interactions: Expression of ACSL3 was also elevated in a panel of ‘androgen-sensitive' (LAPC-4, LNCaP, MDA PCa2a, MDA PCa2b, and 22Rv1) versus ‘androgen-insensitive' (PPC1, PC3, and DU145) prostate cancer cell line
Attard G, Clark J, Ambroisine L, Mills IG, Fisher G, Flohr P, Reid A, Edwards S, Kovacs G, Berney D, Foster C, Massie CE, Fletcher A, De Bono JS, Scardino P, Cuzick J. Heterogeneity and clinical significance of ETV1 translocations in human prostate cancer / Br J Cancer., v.99, issue 2, July, 2008, pp.314-20
Sentences: The presence of the ACSL3:ETV1 fusion was confirmed in this specimen by RT–PCR using 5′-ACSL3 and 3′-ETV1 primers (Figure 3B, C) and co-localisation by FISH of BAC probes corresponding to 5′-ACSL3 sequences (green) and 3′-ETV1 sequences (red) (Figure 3D, panel iii).
Interactions: We found that co-expression of Dyrk1 and Gli1 strongly induced Gli1-dependent gene transcription in the presence of the 3′GliBS-Luc reporter construct, but not in the presence of the mutant reporter construct, m3′GliBS-Luc
Bridge JA, Sanders K, Huang D, Nelson M, Neff JR, Muirhead D, Walker C, Seemayer TA, Sumegi J. Pericytoma with t(7;12) and ACTB-GLI1 fusion arising in bone / Hum Pathol, v.43, issue 9, May, 2012, pp.1524-9
Sentences: Subsequent molecular studies confirmed the presence of an associated ACTB-GLI1 fusion transcript.
Burmeister T, Meyer C, Schwartz S, Hofmann J, Molkentin M, Kowarz E, Schneider B, Raff T, Reinhardt R, Gökbuget N, Hoelzer D, Thiel E, Marschalek R. Recurrent MALAT1-GLI1 oncogenic fusion and GLI1 upregulation define a subset of plexiform fibromyxoma / J Pathol., v.-, issue -, April, 2016, pp.1-9
Sentences: As a positive control with known GLI1 overexpression, a pericytoma carrying t(7;12)(p22;q13) and ACTB–GLI1 fusion showed diffuse cytoplasmic and nuclear immunopositivity
Dahlén A, Fletcher CD, Mertens F, Fletcher JA, Perez-Atayde AR, Hicks MJ, Debiec-Rychter M, Sciot R, Wejde J, Wedin R, Mandahl N, Panagopoulos I. Activation of the GLI Oncogene through Fusion with the β-Actin Gene (ACTB) in a Group of Distinctive Pericytic Neoplasms / Am J Pathol., v.164, issue 5, May, 2004, pp.1645-53
Sentences: Reverse transcriptase (RT) PCR was used for the detection of the ACTB-GLI and the reciprocal GLI-ACTB fusion transcripts.
Castro E, Santiago NC, Ferguson LM, Rao PH, Venkatramani R, López-Terrada D. Translocation t(7;12) as the sole chromosomal abnormality resulting in ACTB-GLI1 fusion in pediatric gastric pericytoma / Hum Pathol, v.53, issue -, July, 2016, pp.137-41
Sentences: We hereby report an unusual gastric tumor arising from the pyloric wall of the stomach in a 9-year old child harboring the exceptionally rare translocation t(7;12) resulting in ACTB-GLI1 gene fusion
Dahlén A, Mertens F, Mandahl N, Panagopoulos I. Molecular genetic characterization of the genomic ACTB-GLI fusion in pericytoma with t(7;12) / Biochem Biophys Res Commun., v.325, issue 4, December, 2004, pp.1318-23
Sentences: Recently, we reported the structure of the ACTB-GLI and GLI-ACTB fusion transcripts in five cases, and herein the corresponding genomic breakpoints were investigated.
Interactions: Recently, Ehrlicher and Pollak et al. demonstrated that in FSGS, a K255E mutation in ACTN4 changes the cellular biological properties in which increasing the affinity for actin increases cellular forces and work and decreases cellular movement
Yang JJ, Park TS, Lee ST, Seo JY, Oh SH, Cho EH, Burmeister T, Ludwig WD, Meyer C, Marschalek R, Kim HJ, Kim SH. Molecular characterization and clinical course of MLL-ACTN4 rearrangement in therapy-related hematologic malignancies / Haematologica, v.99, issue 4, February, 2014, pp.E49-51
Sentences: Size and location of functional domains of the MLL wt, ACTN4 wt, and of the MLL-ACTN4 fusion protein.
Honda K. The biological role of actinin-4 (ACTN4) in malignant phenotypes of cancer / Cell Biosci., v.5, issue -, August, 2015, pp.41
Sentences: Identification of the fusion gene MLL-ACTN4 in adult CD10-negative B-cell precursor acute lymphoblastic leukemia
. A MLL-KIAA0284 fusion gene in a patient with secondary acute myeloid leukemia and t(11;14)(q23;q32) / Blood Cells Mol Dis, v.41, issue 2, Sept-Oct, 2008, pp.210-4
Sentences: To our knowledge, these are the only reported cases of MLL-ACTN4 rearrangement so far, and thus a comprehensive analysis of these 2 MLL-ACTN4 cases possibly provides an insight into this rare MLL rearrangement.
Burmeister T, Meyer C, Schwartz S, Hofmann J, Molkentin M, Kowarz E, Schneider B, Raff T, Reinhardt R, Gökbuget N, Hoelzer D, Thiel E, Marschalek R. The MLL recombinome of adult CD10-negative B-cell precursor acute lymphoblastic leukemia: results from the GMALL study group / Blood, v.113, issue 17, April, 2009, pp.4011-5
Sentences: One patient had an MLL-ACTN4 fusion, 2 others an MLL-TET1 fusion
Yamamoto K, Kawamoto S, Kakiuchi S, Yakushijin K, Matsuoka H, Minami H. Translocation t(11;19)(q23;q13.1) without MLL Rearrangement in Acute Myeloid Leukemia: Heterogeneity of the 11q23 Breakpoints / Acta Haematol, v.134, issue 2, April, 2015, pp.76-9
Sentences: In line with a previously reported case of therapy-related pre-B ALL of unknown karyotype, they found that MLL/ACTN4 rearrangements appear to be therapy-related events.
Keefe JG, Sukov WR, Knudson RA, Nguyen LP, Williamson C, Sinnwell JP, Ketterling RP. Development of five dual-color, double-fusion fluorescence in situ hybridization assays for the detection of common MLL translocation partners / J Mol Diagn, v.12, issue 4, June, 2010, pp.441-52
Sentences: Five translocations account for approximately 80% of MLL rearrangements: t(4;11)(q21;q23), AFF1/MLL; t(6;11)(q27;q23), MLLT4/MLL; t(9;11)(p22;q23), MLLT3/MLL; t(11;19)(q23;p13.1), MLL/ELL; and t(11;19)(q23;p13.3), MLL/MLLT1.
König M, Reichel M, Marschalek R, Haas OA, Strehl S. A highly specific and sensitive fluorescence in situ hybridization assay for the detection of t(4;11)(q21;q23) and concurrent submicroscopic deletions in acute leukaemias / N Engl J Med., v.116, issue 4, March, 2002, pp.758-64
Sentences: On the molecular level, the MLL gene on 11q23 is fused to the AF4 gene in the 4q21 region, resulting in a chimaeric MLL/AF4 fusion transcript.
Frestedt JL, Hilden JM, Moore RO, Kersey JH. Differential expression of AF4/FEL mRNA in human tissues / Genet Anal., v.12, issue 3-4, January, 1996, pp.147-9
Sentences: AF4 mRNA is highly expressed in normal placental tissue which correlates with the newborn age of patients presenting with leukemia characterized by the MLL/AF4 gene rearrangement.
Pane F, Intrieri M, Izzo B, Quintarelli C, Vitale D, Migliorati R, Sebastio L, Salvatore F. A novel MLL/AF4 fusion gene lacking the AF4 transactivating domain in infant acute lymphoblastic leukemia / Blood, v.100, issue 12, December, 2002, pp.4247-8
Sentences: Because the MLL partner fragment included a sequence homologous toAF4 exon 11, we designed a new antisense primer on this exon to amplify the junction sequences of MLL/AF4cDNA, transcribed from the new MLL/AF4 fusion gene.
Domer PH, Fakharzadeh SS, Chen CS, Jockel J, Johansen L, Silverman GA, Kersey JH, Korsmeyer SJ. Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product / Proc Natl Acad Sci U S A., v.90, issue 16, August, 1993, pp.7884-8
Sentences: The composition of the complete MLL-AF4 fusion product argues that it may act through either a gain-of-function or a dominant negative mechanism in leukemogenesis.
Caslini C, Serna A, Rossi V, Introna M, Biondi A. Modulation of cell cycle by graded expression of MLL-AF4 fusion oncoprotein / Leukemia., v.18, issue 6, June, 2004, pp.1064-71
Sentences: Our results demonstrate a dosage-dependent effect of MLL-AF4 fusion oncoprotein on cell cycle progression, with increasing expression levels resulting in the accumulation in G1, prolonged doubling time, both findings that might be responsible for the increased resistance to etoposide-mediated cytotoxicity.
Bertrand FE, Spengeman JD, Shah N, LeBien TW. B-cell development in the presence of the MLL/AF4 oncoprotein proceeds in the absence of HOX A7 and HOX A9 expression / Leukemia., v.17, issue 12, December, 2003, pp.2454-9
Sentences: Infant acute lymphoblastic leukemia (ALL) is frequently characterized by the t(4;11)(q21;q23) cytogenetic abnormality encoding the MLL/AF4 oncogene, increased HOX gene expression and a pro-B/monocytoid phenotype.
Yamamoto S, Zaitsu M, Ishii E, Yatsuki H, Mizutani S, Eguchi M, Ihara K, Okamura T, Hara T, Miyazaki S. High frequency of fusion transcripts of exon 11 and exon 4/5 in AF-4 gene is observed in cord blood, as well as leukemic cells from infant leukemia patients with t(4;11)(q21;q23) / Leukemia., v.12, issue 9, September, 1998, pp.1398-403
Sentences: We analyzed the presence and frequency of the MLL/AF-4 rearrangement in normal cord blood.
Divoky V, Trka JM, Watzinger F, Lion T. Cryptic splice site activation during RNA processing of MLL/AF4 chimeric transcripts in infants with t(4;11) positive ALL / Gene, v.247, issue 1-2, April, 2000, pp.111-8
Sentences: Co-expression of multiple variants of the MLL/AF4 fusion transcript is a common phenomenon in patients with acute lymphoblastic leukemia (ALL) with t(4;11)(q21;q23).
Blütters-Sawatzki R, Borkhardt A, Grathwohl J, Repp R, Rheinisch-Becker I, Bohle RM, Lampert F. Secondary acute myeloid leukemia with translocation (4;11) and MLL/AF4 rearrangement in a 15-year-old boy treated for common acute lymphoblastic leukemia 11 years earlier / Ann Hematol., v.70, issue 1, January, 1995, pp.31-5
Sentences: A polymerase chain reaction assay of a peripheral blood sample recognized the mRNA fusion region for the MLL/AF4 rearrangement, i.e., the molecular equivalent of the translocation (4;11)(q21,q23).
Bizarro S, Cerveira N, Correia C, Lisboa S, Peixoto A, Norton L, Teixeira MR. Molecular characterization of a rare MLL-AF4 (MLL-AFF1) fusion rearrangement in infant leukemia / Cancer Genet Cytogenet., v.178, issue 1, October, 2007, pp.61-4
Sentences: We characterize at both the DNA and RNA level a rare MLL-AF4 fusion transcript identified in a 15-month-old girl with acute lymphoblastic leukemia.
Benedikt A, Baltruschat S, Scholz B, Bursen A, Arrey TN, Meyer B, Varagnolo L, Müller AM, Karas M, Dingermann T, Marschalek R. The leukemogenic AF4-MLL fusion protein causes P-TEFb kinase activation and altered epigenetic signatures / Leukemia., v.25, issue 1, January, 2011, pp.135-44
Sentences: Expression of the AF4-MLL fusion protein in murine hematopoietic progenitor/stem cells results in the development of proB acute lymphoblastic leukemia
Interactions: Several genes involved in fusions have been reported to be fused or rearranged in other cases–AGPAT5, NOTCH2, PUM1, SEC22B, SGK1 and TRERF1 (all early or unclassified), while several are mutated at sequence level, notably SYNE2
Nemoto N, Nemoto N, Suzukawa K, Suzukawa K, Shimizu S, Shimizu S, Shinagawa A, Shinagawa A, Takei N, Takei N, Taki T, Taki T, Hayashi Y, Hayashi Y, Kojima H, Kojima H, Kawakami Y, Kawakami Y, Nagasawa T, Nagasawa T. The relative timing of mutations in a breast cancer genome / PLoS One, v.8, issue 6, June, 2013, pp.e64991
Sentences: Seven of the twelve fusion transcripts were classified as before endoreduplication; two, CTCF-SCUBE2 and BC041478-EXOSC10 were classified later. AGPAT5-MCPH1 and SUSD1-ROD1/PTBP3 and KLK5-CDH23 were undetermined, as their allelic copy number could not be resolved by array CGH or FISH. These structural rearrangements gave rise to at least twelve expressed fusion transcripts, confirmed by RT-PCR and Sanger sequencing: RGS22-SYCP1, CTAGE5-SIP1, PLXND1-TMCC1, SEC22B-NOTCH2, KLK5-CDH23, BC041478-EXOSC10, AGPAT5-MCPH1, SUSD1-ROD1/PTBP3, SGK1-SLC2A12, RHOJ-SYNE2, PUM1-TRERF1 and CTCF-SCUBE2
Interactions: The finding of mutated RAF genes in prostate cancer is consistent with a previous observation that oncogenic BRAFV600E can initiate prostate cancer in mouse models16 and may have major implications for therapy
McMahon M. RAF translocations expand cancer targets / Nat Med., v.16, issue 7, December, 2014, pp.749-750
Sentences: The SCL45A3-BRAF fusion mRNA encodes a 329–amino acid protein that comprises only a C-terminal fragment of BRAF. By contrast, the ESRP1-RAF2 and AGTRAP-BRAF fusions encode proteins with substantial contribution of N-terminal sequences from the RAF fusion partner.
Lee J, Ou SH. Towards the goal of personalized medicine in gastric cancer--time to move beyond HER2 inhibition. Part II: Targeting gene mutations and gene amplifications and the angiogenesis pathway / Discov Med., v.16, issue 86, August, 2013, pp.7-14
Sentences: AGTRAP-BRAF transcript is generated from the fusion of exon 5 of AGTRAP to exon 8 of BRAF with a 597 amino acid AGTRAP-BRAF fusion protein
Nakaoku T, Tsuta K, Ichikawa H, Shiraishi K, Sakamoto H, Enari M, Furuta K, Shimada Y, Ogiwara H, Watanabe S, Nokihara H, Yasuda K, Hiramoto M, Nammo T, Ishigame T, Schetter AJ, Okayama H, Harris CC, Kim YH, Mishima M, Yokota J, Yoshida T, Kohno T. Druggable Oncogene Fusions in Invasive Mucinous Lung Adenocarcinoma / Clin Cancer Res, v.20, issue 12, June, 2014, pp.3087-93
Sentences: These features suggested that the fusion was constitutively active, as in the cases of the ESRP1-BRAF and AGTRAP-BRAF fusions in other cancers
Lee NV, Lira ME, Pavlicek A, Ye J, Buckman D, Bagrodia S, Srinivasa SP, Zhao Y, Aparicio S, Rejto PA, Christensen JG, Ching KA. A novel SND1-BRAF fusion confers resistance to c-Met inhibitor PF-04217903 in GTL16 cells through [corrected] MAPK activation / PLoS One, v.7, issue 6, June, 2012, pp.e39653
Sentences: Similarly, various fusions of BRAF have been implicated in cancer such as pediatric astrocytomas (KIAA1549-BRAF; exons 9/11) , melanocytic nevi (FCHSD1-BRAF; exon 9) , papillary thyroid carcinomas (AKAP9-BRAF; exon 9) , prostate cancer (SLC45A-BRAF; exon 8) , and gastric cancer (AGTRAP-BRAF; exon 8)
Tan P, Yeoh KG. Genetics and Molecular Pathogenesis of Gastric Adenocarcinoma / Gastroenterology., v.149, issue 5, October, 2015, pp.1153-1162
Sentences: An RNA-sequencing study in 2010 revealed for the first time the presence of rare RAF-fusion genes in GC and prostate cancers (eg, AGTRAP-BRAF), and preclinical models expressing these RAF fusions were shown sensitive to treatment by sorafinib, originally designed as a RAF inhibitor
Spans L, Clinckemalie L, Helsen C, Vanderschueren D, Boonen S, Lerut E, Joniau S, Claessens F. The genomic landscape of prostate cancer / Int J Mol Sci., v.14, issue 6, May, 2013, pp.10822-51
Sentences: Paired-end transcriptome sequencing identified several other rearrangements involving genes of the RAF kinase pathway: SLC45A3-BRAF, AGTRAP-BRAF, ESRP1-RAF1, EPB41-BRAF and RAF1-ESRP1
Interactions: The large amplification on chromosomes 7 and 12 could potentially activate the RAS-RAF-MEK pathway by amplification of the BRAF gene located on chromosome 7 or amplification of KRAS located on chromosome 12
Ganly I, Ricarte Filho J, Eng S, Ghossein R, Morris LG, Liang Y, Socci N, Kannan K, Mo Q, Fagin JA, Chan TA. Genomic dissection of Hurthle cell carcinoma reveals a unique class of thyroid malignancy / J Clin Endocrinol Metab., v.98, issue 5, March, 2013, pp.E962-72
Sentences: In addition, common oncogenic fusions of RET and NTRK1 as well as PAX8/PPARγ and AKAP9-BRAF were also assessed by RT-PCR.
Ciampi R, Knauf JA, Kerler R, Gandhi M, Zhu Z, Nikiforova MN, Rabes HM, Fagin JA, Nikiforov YE. Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer / J Clin Invest., v.115, issue 1, January, 2005, pp.94-101
Sentences: The AKAP9-BRAF fusion was preferentially found in radiation-induced papillary carcinomas developing after a short latency, whereas BRAF point mutations were absent in this group.
Ciampi R, Nikiforov YE. Alterations of the BRAF gene in thyroid tumors / Endocr Pathol., v.16, issue 3, 2015, pp.163-72
Sentences: Recently, another mechanism of BRAF activation has been identified, which involves chromosome 7q inversion that results in the AKAP9-BRAF fusion
De Falco V, Giannini R, Tamburrino A, Ugolini C, Lupi C, Puxeddu E, Santoro M, Basolo F. Functional Characterization of the Novel T599I-VKSRdel BRAF Mutation in a Follicular Variant Papillary Thyroid Carcinoma / J Clin Endocrinol Metab., v.93, issue 11, November, 2008, pp.4398-402
Sentences: Less frequent are the K601E (5), V599ins (6), G474R (7), and G469R (8) point mutations as well as complex genetic alterations such as the AKAP9-BRAF rearrangement (9), the V600E-K601del (10, 11), and V600D-FLAGT601–605ins