Skip to main content

Main menu

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Subscribers
    • Advertisers
    • Editorial Board
  • Other Publications
    • In Vivo
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
    • 2008 Nobel Laureates
  • About Us
    • General Policy
    • Contact
  • Other Publications
    • Anticancer Research
    • In Vivo
    • Cancer Genomics & Proteomics

User menu

  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Anticancer Research
  • Other Publications
    • Anticancer Research
    • In Vivo
    • Cancer Genomics & Proteomics
  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Anticancer Research

Advanced Search

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Subscribers
    • Advertisers
    • Editorial Board
  • Other Publications
    • In Vivo
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
    • 2008 Nobel Laureates
  • About Us
    • General Policy
    • Contact
  • Visit us on Facebook
  • Follow us on Linkedin
Research ArticleExperimental Studies

An Unbalanced Chromosome Translocation Between 7p22 and 12q13 Leads to ACTB-GLI1 Fusion in Pericytoma

IOANNIS PANAGOPOULOS, LUDMILA GORUNOVA, TOR VIKAN RISE, KRISTIN ANDERSEN, FRANCESCA MICCI and SVERRE HEIM
Anticancer Research March 2020, 40 (3) 1239-1245; DOI: https://doi.org/10.21873/anticanres.14065
IOANNIS PANAGOPOULOS
1Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: ioannis.panagopoulos@rr-research.no
LUDMILA GORUNOVA
1Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
TOR VIKAN RISE
2Department of Pathology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
KRISTIN ANDERSEN
1Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
FRANCESCA MICCI
1Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
SVERRE HEIM
1Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
3Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Background/Aim: Since the first description of five pericytomas with the t(7;12)/ACTB-GLI1 fusion gene, only three new tumors were studied by both cytogenetics and molecular techniques. We report here genetic data on another case of this rare tumor. Materials and Methods: Cytogenetic, fluorescence in situ hybridization (FISH), reverse transcription polymerase chain reaction (RT-PCR), and Sanger sequencing analyses were performed. Results: The pericytoma carried two structurally rearranged chromosomes: der(7)t(7;12)(p22;q13) and der(12)t(1;12)(q12;q13). In FISH experiments with a break-apart probe for GLI1, the distal part of the probe hybridized to der(7) whereas the proximal part to der(12). RT-PCR and Sanger sequencing detected an ACTB-GLI1 fragment in which exon 2 of ACTB was fused to exon 6 of GLI1. Conclusion: The ACTB-GLI1 fusion gene was mapped at der(7)t(7;12)(p22;q13) and coded for a putative ACTB-GLI1 protein in which the first 41 amino acid (aa) of ACTB replaced the first 177 aa of GLI1.

  • Pericytoma
  • t(7;12)
  • ACTB-GLI1 fusion gene
  • GLI1 isoform 2 protein
  • unbalanced chromosome translocation

Fusion of the genes actin beta (ACTB on 7p22.1) and glioma associated oncogene homologue 1 (GLI1 on 12q13.3) was first reported by Dahlén et al. (1, 2) in five benign spindle cell tumors with distinctive pericytic features and a t(7;12)(p21-22;q13-15) chromosome translocation. The tumors defined a discrete group of previously uncharacterized neoplasms for which the term “pericytoma with t(7;12)” was proposed in order to reflect both the morphological and cytogenetic features (1). Until now, the ACTB-GLI1 fusion gene has been reported in fifteen such cases, four of which had developed metastases (1-7) (Table I). Because of the apparent rarity of tumors carrying a t(7;12)/ACTB-GLI1, we here present the genetic and clinical features of another pericytoma with an unbalanced chromosome translocation between 7p22 and 12q13 leading to an ACTB-GLI1 fusion gene.

Materials and Methods

Case description and pathology. An 83-year-old woman presented with a painless palpable mass in her left thigh. Magnetic resonance imaging (MRI) revealed a 4×11×10 cm encapsulated, mainly cystic tumor in the adductor magnus muscle. There was contrast enhancement in the capsule and a small intracapsular part of the tumor. Staging studies revealed no evidence of metastatic disease. Examination of the core needle biopsy showed a small blue round cell tumor with low mitotic activity. Immunohistochemistry showed that the tumor cells were positive for CD99 (Figure 1A), and fluorescence in situ hybridization (FISH) showed no rearrangement of EWSR1.

Wide tumor excision was performed. Gross examination revealed a cystic tumor with a maximum diameter of 9.5 cm. The cystic tumor was filled with serous fluid and grey, necrotic appearing material. In the internal part of the fibrous capsule, there was a white and solid layer 3-15 mm thick (Figure 1B). The tumor demonstrated sheetlike growth with an intricate network of capillary-sized vessels (Figure 1C). In the fibrous capsule there was evidence of tumor cells around larger vessels (Figure 1D). The neoplastic cells were small and ovoid with sparse eosinophilic cytoplasm and round nuclei with dense chromatin and scattered small white pseudoinclusions. The ratio of mitoses was 1/10 high-power field (HPF), no atypical mitotic figures were noted. Immunohistochemical staining showed that the tumor cells were positive for cluster of differentiation (CD) CD99 (strong membranous, weak cytoplasmic positivity), alpha-smooth muscle actin (SMA weak), cytokeratin AE1/AE3 (CK ae1/ae3 weak and focal), epithelial membrane antigen (EMA weak and focal), and berep4 (weak and focal). Staining for CD34 and CD31 highlighted a prominent thin-walled vasculature, but the tumor cells were negative. The tumor cells were additionally negative for S100, Sox-10, desmin, H-caldesmon, synaptophysin, CD45, CD30, and ETS-related gene protein (ERG).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table I.

The currently reported pericytomas with the ACTB-GLI1 fusion gene including the present tumor.

G-banding and FISH analyses. Fresh tissue from a representative area of the tumor was short-term cultured and analyzed cytogenetically as previously described (8).

FISH was performed on metaphase spreads using the Cytocell CHOP (DDIT3 on 12q13.3) break-apart FISH Probe (Cytocell, Oxford Gene Technology, Begbroke, Oxfordshire, UK). According to the company's information, the CHOP break-apart probe consists of a proximal to the centromere red 146 kb probe and a distal to the centromere green 165 kb probe, which are positioned on each side of the DDIT3 (CHOP) gene. However, the genes INHBC, INHBE, GLI1, ARHGAP9, MARS, DDIT3, and MBD6 map between the red and the green probes. Thus, the probe is not specific for the DDIT3 rearrangement but can be used to investigate possible rearrangements of any of the above-mentioned genes. In the present study, we used it to look for GLI1 rearrangements. Fluorescent signals were captured and analyzed using the CytoVision system (Leica Biosystems, Newcastle, UK).

Reverse transcription (RT) PCR analysis. In order to confirm the presence of an ACTB-GLI1 fusion transcript (see below), reverse transcription (RT) polymerase chain reaction (PCR) and Sanger sequencing analyses were performed as previously described (9). The primers used were the forward ACT61F (5’-CCGCCAGCTCACCATGGATGATG-3’) and the reverse GLI720R (5’-AGGTCCTCCCGCCCATCCAGC-3’) (1). The quality of the cDNA synthesis was assessed by amplification of a cDNA fragment of the ABL protooncogene 1, non-receptor tyrosine kinase (ABL1) gene using the primers ABL1-91F1 (5’-CAGCGGCCAGTAGCATCTGACTTTG-3’) and ABL1-404R1 (5’-CTCAGCAGATACTCAGCGGCATTGC-3’). PCR cycling was at 94°C for 30 s followed by 35 cycles of 7 s at 98°C, 30 s at 60°C, 30 s at 72°C, and a final extension for 5 min at 72°C.

Results

G-banding analysis of short-term cultured cells from the tumor yielded the karyotype 46,XX,der(7)t(7;12)(p22;q13), der(12)t(1;12)(q12;q13)[11]/46,idem,tas(X;8)(q28;q24)[3]/46, idem,tas(8;12)(q24;q24)[2] (Figure 2).

FISH analysis using the CHOP break-apart probe (Figure 3A and B) showed that the distal part of the probe (green signal) hybridized to the der(7)t(7;12)(p22;q13), whereas the proximal part of the probe (red signal) hybridized to der(12)t(1;12)(q12;q13) (Figure 3C).

RT-PCR amplified a 264 bp cDNA fragment. Sanger sequencing showed that it was an ACTB-GLI1 chimeric fragment in which exon 2 of ACTB (nt 207 in the sequence with accession number NM_001101.5) fused with exon 6 of GLI1 (nt 613 in the sequence with accession number NM_005269.2) (Figure 4).

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

Microscopic examination of the pericytoma. A) Immunohistochemical examination showing expression of CD99 in the pericytoma, 40×. B) Hematoxylin and eosin (H&E)-stained section showing area of encapsulated tumor, 1×. C) H&E-stained section showing sheet-like growth with an intricate network of capillary-sized vessels, 40×. D) H&E-stained section showing perivascular orientation of tumor cells, 20×.

Discussion

Since the first description in 2004 of “pericytoma with t(7;12)” in five tumors (1), only three new pericytomas were studied by both cytogenetics and molecular techniques (Table I). On the chromosome level, all eight tumors reported in literature were in diploid range (45-46 chromosomes). Half of the pericytomas had a sole t(7;12), two more tumors carried 1-2 additional changes, whereas the other two had complex karyotypes. All but one tumor showed visibly balanced t(7;12) (Table I).

The present case also had a simple diploid karyotype, accompanied by two subclones with supplementary telomeric associations. The tumor did not carry a balanced t(7;12) chromosome translocation, but instead a der(7)t(7;12)(p22;q13) and a der(12)t(1;12)(q12;q13). The FISH analyses not only supported the cytogenetic data but further located the pathogenetic ACTB-GLI1 fusion gene on the der(7).

The t(7;12) / der(7)t(7;12) places GLI1 under the control of the strong ACTB promoter resulting in activation of GLI1 and deregulation of its downstream targets (1-7, 10, 11). According to the NCBI database, ACTB is ubiquitously expressed in 27 tissue types. The highest expression was found in the appendix having 2395.4 RPKM (Reads Per Kilobase of transcript, per Million mapped reads) whereas the lowest was in the pancreas with 95.5 RPKM (12). In the same 27 tissues, GLI1 is weakly expressed. The highest GLI1 expression was found in the endometrium with 5.6 RPKM followed by expression in the testis (2.9 RPKM) and the gall bladder (2.5 RPKM) (13).

GLI1 together with GLI2 (on 2q14.2), GLI3 (on 7p14.1), and GLI4 (on 8q24.3) make up the GLI family of transcription factors (14). They bind to the DNA consensus sequence 5’-GACCACCCA-3’- in the promoters of target genes regulating their expression (15). The GLI1 protein is a transcription activator, GLI2 is both an activator and a repressor, GLI3 functions as a repressor, whereas there is no information on the function of GLI4 (16). The members of the GLI family are main mediators of the highly conserved Hedgehog signaling pathway, which plays a critical role in embryonic development (17-20). Aberrant Hedgehog signaling is associated with the development and progression of various types of cancer and is implicated in multiple aspects of tumorigenesis (21-27).

Figure 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2.

Karyogram of the pericytoma showing two abnormal chromosomes, der(7)t(7;12)(p22;q13), and der(12)t(1;12)(q12;q13). Breakpoint positions are indicated by arrows.

Three transcript variants have been reported for GLI1. Transcript variant 1 (NM_005269) codes for a 1106 amino acid (aa) protein (NP_005260; isoform 1).

GLI1 isoform 1 contains (from N to C terminal) a Snail/Gfi-1(SNAG) domain, an N-terminal degradation signal, DN degron, an N-terminal binding site for Suppressor of Fused protein (SUFU binding site), a forkhead box protein (FOXP) coiled-coil domain, 5 Cys2-His2 (C2H2) Zn-finger motifs, a nuclear localization signal, a C-terminal degradation signal, Dc degron, a nuclear export signal, a C-terminal SUFU binding site, and the transactivation domain (28-31).

Transcript variant 2 (NM_001160045) lacks the first two coding exons of transcript variant 1, transcription initiation occurs from an internal AUG site, and codes for N-terminally truncated protein isoform 2 (NP_001153517), also known as GLI1DeltaN (32). The GLI1 isoform 2 lacks the first 128 amino acids of GLI1 isoform 1 which contain the SNAG domain, the DN degron, and the SUFU binding site (29, 31, 32). Inhibition of GLI1 activity by the SUFU protein has been reported (29, 30).

The GLI1 transcript variant 3 (NM_001167609) has an in-frame deletion of 123 bases (41 codons) spanning the entire exon 3 and part of exon 4 of the GLI1 gene (33). This transcript codes for the GLI1 isoform 3 protein (NP_001161081), also known as tGLI1 (33). GLI1 transcript variant 3 was highly expressed in glioblastoma multiforme and other cancers but has not been detected in normal cells. It promotes cancer cell migration and activates a different set of genes from those activated by GLI1 isoform 1 (33).

The chimeric ACTB-GLI1 transcript described here is an in-frame fusion of exon 2 of ACTB with exon 6 of GLI1 coding for a putative 969 aa protein in which the first 177 aa of GLI1 are replaced with the first 41 aa of ACTB. In fact, in all reported ACTB-GLI1 chimeric transcripts, exons 1, 2, or 3 of ACTB are fused to exons 5, 6 (most commonly), or 7 of GLI1 (1, 3-5, 7).

Figure 3.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 3.

FISH analysis of the pericytoma with the Cytocell CHOP (DDIT3) (12q13.3) break-apart FISH Probe. A) Ideogram of chromosome 12 showing the mapping position of the FISH probe. B) Diagram showing the FISH probe and the genes covered by the probe. C) FISH on a metaphase spread showing that the distal part of the probe (green signal) hybridized to the der(7)t(7;12)(p22;q13) whereas the proximal part of the probe (red signal) hybridized to der(12)t(1;12)(q12;q13). Both distal and proximal parts of the probe hybridized to the normal chromosome 12.

Figure 4.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 4.

RT-PCR and Sanger sequencing. A) Gel electrophoresis showing the amplified ACTB-GLI1 cDNA fragment using the primer combination ACT61F/ GLI720R (lane 1) and an amplified ABL1 cDNA using the primers ABL1-91F1 and ABL1-404R1 (lane 2). M, GeneRuler 1 Kb Plus DNA ladder (ThermoFisher Scientific). B) Partial sequence chromatograms of the cDNA amplified fragment showing the junction position of exon 2 of ACTB with exon 6 of GLI1.

Recently, the MALAT1-GLI1 fusion gene was reported in a subset of plexiform fibromyxomas, in gastroblastomas, and in epithelioid tumors with metastatic potential (5, 34, 35). The MALAT1 gene (on 11q13.1) is ubiquitously expressed and produces a long non-coding RNA (36, 37). Part of MALAT1 was fused to exon 6 (plexiform fibromyxomas) or to the last 19 nt of the 145 bp long exon 5 (gastroblastoma) of GLI1 (34, 35). Spans et al. (34) showed that the truncated GLI1 protein (lacking exons 1–5) was transcriptionally active.

A PTCH1-GLI1 fusion has also been found in an epithelioid tumor with metastatic potential (5). In that case, exon 1C of PTCH1 fused to exon 7 of GLI1 (PTCH1 transcript variant 1a, accession number NM_001083602.2) (38, 39). The only contribution of exon 1C PTCH1 was the initiation ATG codon. Expression of exon 1C of PTCH1 was reported to be tissue specific, found in the adult brain, placenta, lung, kidney, pancreas, and in fetal kidney (38).

Taking the information reviewed above into consideration, we conclude that the ACTB-GLI1, MALAT1-GLI1, and PTCH1-GLI1 fusion genes code for proteins which are similar to the GLI1 isoform 2 protein. They contain the GLI1 FOXP coiled-coil domain, the 5 C2H2 Zn-finger motifs, the nuclear localization signal, the C-terminal degradation signal, Dc degron, nuclear export signal, the C-terminal SUFU binding site, and the transactivation domain. They will lack the SNAG domain, the N-terminal degradation signal, DN degron, and the N-terminal SUFU binding site. The expression of these proteins will be controlled by strong (ACTB and MALAT1) or tissue specific (PTCH1) promoters.

Acknowledgements

This work was supported by grants from Radiumhospitalets Legater.

Footnotes

  • Authors' Contributions

    IP designed and supervised the research, performed molecular genetic experiments, bioinformatics analysis, and wrote the article. LG performed cytogenetic analysis and evaluated the FISH data. TVR performed the pathological examination. KA performed molecular genetic experiments, FISH analysis, and evaluated the data. FM supervised the research. SH assisted with experimental design and writing of the article. All Authors read and approved the final article.

  • This article is freely accessible online.

  • Conflicts of Interest

    The Authors declare that no potential conflicts of interest exist.

  • Received January 23, 2020.
  • Revision received February 2, 2020.
  • Accepted February 3, 2020.
  • Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved

References

  1. ↵
    1. Dahlén A,
    2. Fletcher CD,
    3. Mertens F,
    4. Fletcher JA,
    5. Perez-Atayde AR,
    6. Hicks MJ,
    7. Debiec-Rychter M,
    8. Sciot R,
    9. Wejde J,
    10. Wedin R,
    11. Mandahl N,
    12. Panagopoulos I
    : Activation of the GLI oncogene through fusion with the beta-actin gene (ACTB) in a group of distinctive pericytic neoplasms: pericytoma with t(7;12). Am J Pathol 164(5): 1645-1653, 2004. PMID: 15111311. DOI: 10.1016/s0002-9440(10)63723-6
    OpenUrlPubMed
  2. ↵
    1. Dahlén A,
    2. Mertens F,
    3. Mandahl N,
    4. Panagopoulos I
    : Molecular genetic characterization of the genomic ACTB-GLI fusion in pericytoma with t(7;12). Biochem Biophys Res Commun 325(4): 1318-1323, 2004. PMID: 15555571. DOI: 10.1016/j.bbrc.2004.10.172
    OpenUrlPubMed
  3. ↵
    1. Bridge JA,
    2. Sanders K,
    3. Huang D,
    4. Nelson M,
    5. Neff JR,
    6. Muirhead D,
    7. Walker C,
    8. Seemayer TA,
    9. Sumegi J
    : Pericytoma with t(7;12) and ACTB-GLI1 fusion arising in bone. Hum Pathol 43(9): 1524-1529, 2012. PMID: 22575261. DOI: 10.1016/j.humpath.2012.01.019
    OpenUrlPubMed
    1. Castro E,
    2. Cortes-Santiago N,
    3. Ferguson LM,
    4. Rao PH,
    5. Venkatramani R,
    6. Lopez-Terrada D
    : Translocation t(7;12) as the sole chromosomal abnormality resulting in ACTB-GLI1 fusion in pediatric gastric pericytoma. Hum Pathol 53:137-141, 2016. PMID: 26980027. DOI: 10.1016/j.humpath.2016.02.015
    OpenUrl
  4. ↵
    1. Antonescu CR,
    2. Agaram NP,
    3. Sung YS,
    4. Zhang L,
    5. Swanson D,
    6. Dickson BC
    : A distinct malignant epithelioid neoplasm with GLI1 gene rearrangements, frequent S100 protein expression, and metastatic potential: Expanding the spectrum of pathologic entities with ACTB/MALAT1/PTCH1-GLI1 fusions. Am J Surg Pathol 42(4): 553-560, 2018. PMID: 29309307. DOI: 10.1097/PAS.0000000000001010
    OpenUrl
    1. Kerr DA,
    2. Pinto A,
    3. Subhawong TK,
    4. Wilky BA,
    5. Schlumbrecht MP,
    6. Antonescu CR,
    7. Nielsen GP,
    8. Rosenberg AE
    : Pericytoma with t(7;12) and ACTB-GLI1 fusion: Reevaluation of an unusual entity and its relationship to the spectrum of GLI1 fusion-related neoplasms. Am J Surg Pathol 43(12): 1682-1692, 2019. PMID: 31567194. DOI: 10.1097/PAS.0000000000001360
    OpenUrl
  5. ↵
    1. Koh NWC,
    2. Seow WY,
    3. Lee YT,
    4. Lam JCM,
    5. Lian DWQ
    : Pericytoma with t(7;12): The first ovarian case reported and a review of the literature. Int J Gynecol Pathol 38(5): 479-484, 2019. PMID: 30085941. DOI: 10.1097/PGP.0000000000000542
    OpenUrl
  6. ↵
    1. Panagopoulos I,
    2. Gorunova L,
    3. Andersen HK,
    4. Pedersen TD,
    5. Lomo J,
    6. Lund-Iversen M,
    7. Micci F,
    8. Heim S
    : Genetic characterization of myoid hamartoma of the breast. Cancer Genomics Proteomics 16(6): 563-568, 2019. PMID: 31659109. DOI: 10.21873/cgp.20158
    OpenUrlAbstract/FREE Full Text
  7. ↵
    1. Panagopoulos I,
    2. Lobmaier I,
    3. Gorunova L,
    4. Heim S
    : Fusion of the genes WWTR1 and FOSB in pseudomyogenic hemangioendothelioma. Cancer Genomics Proteomics 16(4): 293-298, 2019. PMID: 31243110. DOI: 10.21873/cgp.20134
    OpenUrlAbstract/FREE Full Text
  8. ↵
    1. Ng SY,
    2. Gunning P,
    3. Eddy R,
    4. Ponte P,
    5. Leavitt J,
    6. Shows T,
    7. Kedes L
    : Evolution of the functional human beta-actin gene and its multi-pseudogene family: conservation of noncoding regions and chromosomal dispersion of pseudogenes. Mol Cell Biol 5(10): 2720-2732, 1985. PMID: 3837182. DOI: 10.1128/mcb.5.10.2720
    OpenUrlAbstract/FREE Full Text
  9. ↵
    1. Ng SY,
    2. Gunning P,
    3. Liu SH,
    4. Leavitt J,
    5. Kedes L
    : Regulation of the human beta-actin promoter by upstream and intron domains. Nucleic Acids Res 17(2): 601-615, 1989. PMID: 2915924. DOI: 10.1093/nar/17.2.601
    OpenUrlCrossRefPubMed
  10. ↵
    1. National Center for Biotechnology Information
    : ACTB actin beta [Homo sapiens (human)], 2020. Available at: https://www.ncbi.nlm.nih.gov/gene/60#gene-expression (Last accessed on 5th January 2020)
  11. ↵
    1. National Center for Biotechnology Information
    : GLI1 GLI family zinc finger 1 [Homo sapiens (human)], 2020 Available at: https://www.ncbi.nlm.nih.gov/gene/60#gene-expression (Last accessed on 13th January 2020)
  12. ↵
    1. Ruppert JM,
    2. Kinzler KW,
    3. Wong AJ,
    4. Bigner SH,
    5. Kao FT,
    6. Law ML,
    7. Seuanez HN,
    8. O'Brien SJ,
    9. Vogelstein B
    : The GLI-Kruppel family of human genes. Mol Cell Biol 8(8): 3104-3113, 1988. PMID: 2850480. DOI: 10.1128/mcb.8.8.3104
    OpenUrlAbstract/FREE Full Text
  13. ↵
    1. Kinzler KW,
    2. Vogelstein B
    : The GLI gene encodes a nuclear protein which binds specific sequences in the human genome. Mol Cell Biol 10(2): 634-642, 1990. PMID: 2105456. DOI: 10.1128/mcb.10.2.634
    OpenUrlAbstract/FREE Full Text
  14. ↵
    1. Palle K,
    2. Mani C,
    3. Tripathi K,
    4. Athar M
    : Aberrant GLI1 Activation in DNA damage response, carcinogenesis and chemoresistance. Cancers (Basel) 7(4): 2330-2351, 2015. PMID: 26633513. DOI: 10.3390/cancers7040894
    OpenUrl
  15. ↵
    1. Ingham PW,
    2. McMahon AP
    : Hedgehog signaling in animal development: paradigms and principles. Genes Dev 15(23): 3059-3087, 2001. PMID: 11731473. DOI: 10.1101/gad.938601
    OpenUrlFREE Full Text
    1. Armas-Lopez L,
    2. Zuniga J,
    3. Arrieta O,
    4. Avila-Moreno F
    : The Hedgehog-GLI pathway in embryonic development and cancer: implications for pulmonary oncology therapy. Oncotarget 8(36): 60684-60703, 2017. PMID: 28948003. DOI: 10.18632/oncotarget.19527
    OpenUrl
    1. Carballo GB,
    2. Honorato JR,
    3. de Lopes GPF,
    4. Spohr T
    : A highlight on Sonic hedgehog pathway. Cell Commun Signal 16(1): 11, 2018. PMID: 29558958. DOI: 10.1186/s12964-018-0220-7
    OpenUrlCrossRefPubMed
  16. ↵
    1. Sabol M,
    2. Trnski D,
    3. Musani V,
    4. Ozretic P,
    5. Levanat S
    : Role of GLI transcription factors in pathogenesis and their potential as new therapeutic targets. Int J Mol Sci 19(9), 2018. PMID: 30158435. DOI: 10.3390/ijms19092562
  17. ↵
    1. Thayer S
    : The emerging role of the hedgehog signaling pathway in gastrointestinal cancers. Clin Adv Hematol Oncol 2(1): 17, 20, 63, 2004. PMID: 16163153.
    OpenUrlPubMed
    1. Caro I,
    2. Low JA
    : The role of the hedgehog signaling pathway in the development of basal cell carcinoma and opportunities for treatment. Clin Cancer Res 16(13): 3335-3339, 2010. PMID: 20439455. DOI: 10.1158/1078-0432.CCR-09-2570
    OpenUrlAbstract/FREE Full Text
    1. Cochrane CR,
    2. Szczepny A,
    3. Watkins DN,
    4. Cain JE
    : Hedgehog signaling in the maintenance of cancer stem cells. Cancers (Basel) 7(3): 1554-1585, 2015. PMID: 26270676. DOI: 10.3390/cancers7030851
    OpenUrl
    1. Fattahi S,
    2. Pilehchian Langroudi M,
    3. Akhavan-Niaki H
    : Hedgehog signaling pathway: Epigenetic regulation and role in disease and cancer development. J Cell Physiol 233(8): 5726-5735, 2018. PMID: 29380372. DOI: 10.1002/jcp.26506
    OpenUrl
    1. Sari IN,
    2. Phi LTH,
    3. Jun N,
    4. Wijaya YT,
    5. Lee S,
    6. Kwon HY
    : Hedgehog signaling in cancer: a prospective therapeutic target for eradicating cancer stem cells. Cells 7(11), 2018. PMID: 30423843. DOI: 10.3390/cells7110208
    1. Skoda AM,
    2. Simovic D,
    3. Karin V,
    4. Kardum V,
    5. Vranic S,
    6. Serman L
    : The role of the Hedgehog signaling pathway in cancer: A comprehensive review. Bosn J Basic Med Sci 18(1): 8-20, 2018. PMID: 29274272. DOI: 10.17305/bjbms.2018.2756
    OpenUrl
  18. ↵
    1. Pietrobono S,
    2. Gagliardi S,
    3. Stecca B
    : Non-canonical Hedgehog signaling pathway in cancer: Activation of GLI transcription factors beyond smoothened. Front Genet 10: 556, 2019. PMID: 31244888. DOI: 10.3389/fgene.2019.00556
    OpenUrl
  19. ↵
    1. Yoon JW,
    2. Liu CZ,
    3. Yang JT,
    4. Swart R,
    5. Iannaccone P,
    6. Walterhouse D
    : GLI activates transcription through a herpes simplex viral protein 16-like activation domain. J Biol Chem 273(6): 3496-3501, 1998. PMID: 9452474. DOI: 10.1074/jbc.273.6.3496
    OpenUrlAbstract/FREE Full Text
  20. ↵
    1. Dunaeva M,
    2. Michelson P,
    3. Kogerman P,
    4. Toftgard R
    : Characterization of the physical interaction of Gli proteins with SUFU proteins. J Biol Chem 278(7): 5116-5122, 2003. PMID: 12426310. DOI: 10.1074/jbc.M209492200
    OpenUrlAbstract/FREE Full Text
  21. ↵
    1. Merchant M,
    2. Vajdos FF,
    3. Ultsch M,
    4. Maun HR,
    5. Wendt U,
    6. Cannon J,
    7. Desmarais W,
    8. Lazarus RA,
    9. de Vos AM,
    10. de Sauvage FJ
    : Suppressor of fused regulates Gli activity through a dual binding mechanism. Mol Cell Biol 24(19): 8627-8641, 2004. PMID: 15367681. DOI: 10.1128/MCB.24.19.8627-8641.2004
    OpenUrlAbstract/FREE Full Text
  22. ↵
    1. Huntzicker EG,
    2. Estay IS,
    3. Zhen H,
    4. Lokteva LA,
    5. Jackson PK,
    6. Oro AE
    : Dual degradation signals control Gli protein stability and tumor formation. Genes Dev 20(3): 276-281, 2006. PMID: 16421275. DOI: 10.1101/gad.1380906
    OpenUrlAbstract/FREE Full Text
  23. ↵
    1. Shimokawa T,
    2. Tostar U,
    3. Lauth M,
    4. Palaniswamy R,
    5. Kasper M,
    6. Toftgard R,
    7. Zaphiropoulos PG
    : Novel human glioma-associated oncogene 1 (GLI1) splice variants reveal distinct mechanisms in the terminal transduction of the hedgehog signal. J Biol Chem 283(21): 14345-14354, 2008. PMID: 18378682. DOI: 10.1074/jbc.M800299200
    OpenUrlAbstract/FREE Full Text
  24. ↵
    1. Lo HW,
    2. Zhu H,
    3. Cao X,
    4. Aldrich A,
    5. Ali-Osman F
    : A novel splice variant of GLI1 that promotes glioblastoma cell migration and invasion. Cancer Res 69(17): 6790-6798, 2009. PMID: 19706761. DOI: 10.1158/0008-5472.CAN-09-0886
    OpenUrlAbstract/FREE Full Text
  25. ↵
    1. Spans L,
    2. Fletcher CD,
    3. Antonescu CR,
    4. Rouquette A,
    5. Coindre JM,
    6. Sciot R,
    7. Debiec-Rychter M
    : Recurrent MALAT1-GLI1 oncogenic fusion and GLI1 up-regulation define a subset of plexiform fibromyxoma. J Pathol 239(3): 335-343, 2016. PMID: 27101025. DOI: 10.1002/path.4730
    OpenUrlCrossRefPubMed
  26. ↵
    1. Graham RP,
    2. Nair AA,
    3. Davila JI,
    4. Jin L,
    5. Jen J,
    6. Sukov WR,
    7. Wu TT,
    8. Appelman HD,
    9. Torres-Mora J,
    10. Perry KD,
    11. Zhang L,
    12. Kloft-Nelson SM,
    13. Knudson RA,
    14. Greipp PT,
    15. Folpe AL
    : Gastroblastoma harbors a recurrent somatic MALAT1-GLI1 fusion gene. Mod Pathol 30(10): 1443-1452, 2017. PMID: 28731043. DOI: 10.1038/modpathol.2017.68
    OpenUrlCrossRefPubMed
  27. ↵
    1. Zhang X,
    2. Hamblin MH,
    3. Yin KJ
    : The long noncoding RNA Malat1: Its physiological and pathophysiological functions. RNA Biol 14(12): 1705-1714, 2017. PMID: 28837398. DOI: 10.1080/15476286.2017.1358347
    OpenUrlCrossRef
  28. ↵
    1. Zhao M,
    2. Wang S,
    3. Li Q,
    4. Ji Q,
    5. Guo P,
    6. Liu X
    : MALAT1: A long non-coding RNA highly associated with human cancers. Oncol Lett 16(1): 19-26, 2018. PMID: 29928382. DOI: 10.3892/ol.2018.8613
    OpenUrl
  29. ↵
    1. Shimokawa T,
    2. Rahnama F,
    3. Zaphiropoulos PG
    : A novel first exon of the Patched1 gene is upregulated by Hedgehog signaling resulting in a protein with pathway inhibitory functions. FEBS Lett 578(1-2): 157-162, 2004. PMID: 15581634. DOI: 10.1016/j.febslet.2004.11.006
    OpenUrlCrossRefPubMed
  30. ↵
    1. Shimokawa T,
    2. Svard J,
    3. Heby-Henricson K,
    4. Teglund S,
    5. Toftgard R,
    6. Zaphiropoulos PG
    : Distinct roles of first exon variants of the tumor-suppressor Patched1 in Hedgehog signaling. Oncogene 26(34): 4889-4896, 2007. PMID: 17310997. DOI: 10.1038/sj.onc.1210301
    OpenUrlCrossRefPubMed
PreviousNext
Back to top

In this issue

Anticancer Research: 40 (3)
Anticancer Research
Vol. 40, Issue 3
March 2020
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Back Matter (PDF)
  • Ed Board (PDF)
  • Front Matter (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on Anticancer Research.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
An Unbalanced Chromosome Translocation Between 7p22 and 12q13 Leads to ACTB-GLI1 Fusion in Pericytoma
(Your Name) has sent you a message from Anticancer Research
(Your Name) thought you would like to see the Anticancer Research web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
2 + 6 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
An Unbalanced Chromosome Translocation Between 7p22 and 12q13 Leads to ACTB-GLI1 Fusion in Pericytoma
IOANNIS PANAGOPOULOS, LUDMILA GORUNOVA, TOR VIKAN RISE, KRISTIN ANDERSEN, FRANCESCA MICCI, SVERRE HEIM
Anticancer Research Mar 2020, 40 (3) 1239-1245; DOI: 10.21873/anticanres.14065

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Reprints and Permissions
Share
An Unbalanced Chromosome Translocation Between 7p22 and 12q13 Leads to ACTB-GLI1 Fusion in Pericytoma
IOANNIS PANAGOPOULOS, LUDMILA GORUNOVA, TOR VIKAN RISE, KRISTIN ANDERSEN, FRANCESCA MICCI, SVERRE HEIM
Anticancer Research Mar 2020, 40 (3) 1239-1245; DOI: 10.21873/anticanres.14065
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgements
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • 5-Azacytidine (5-aza) Induces p53-associated Cell Death Through Inhibition of DNA Methyltransferase Activity in Hep3B and HT-29 Cells
  • Prognostic Value of WNT1, NOTCH1, PDGFRβ, and CXCR4 in Oral Squamous Cell Carcinoma
  • Hypoxia-adapted Multiple Myeloma Stem Cells Resist γδ-T-Cell-mediated Killing by Modulating the Mevalonate Pathway
Show more Experimental Studies

Similar Articles

Keywords

  • Pericytoma
  • t(7;12)
  • ACTB-GLI1 fusion gene
  • GLI1 isoform 2 protein
  • unbalanced chromosome translocation
Anticancer Research

© 2023 Anticancer Research

Powered by HighWire