Soft Tissues: Lipoblastoma with t(2;8)(q32;q12.1) COL3A1/PLAG1
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| Written | 2014-10 | Hideki Yoshida, Mitsuru Miyachi, Hajime Hosoi |
| Department of Pediatrics, Graduate School of MedicalScience, Kyoto Prefectural University of Medicine, Kajii-cho Hirokoji, Kamigyo-ku, Kyoto, Japan, E-mail address: hhosoi@koto.kpu-m.ac.jp |
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1. Abstract
| Abstract | Review on lipoblastoma with t(2;8)(q32;q12.1) COL3A1/PLAG1, with data on clinics, and the genes involved. |
2. Identity
| Atlas_Id | 6626 |
| Phylum | Soft Tissues::Lipoblastoma |
| WHO/OMS Classification | Soft Tissues |
3. Clinics and Pathology
| Disease | |
4. Cytogenetics
| Cytogenetics Morphological | t(2;8)(q32;q12.1) |
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| t(2;8)(q32;q12) G- banding: - Courtesy Galina Aldrete and Charles D. Bangs | |
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| PLAG1 FISH of formalin-fixed paraffin-embedded section showing PLAG1 rearrangement: - Courtesy Gail Aldrete and Charles D. Bangs | |
5. Genes involved and Proteins
| Gene Name | COL3A1 (collagen type III alpha 1 chain) |
| Location | 2q32.2 |
| Note | Mutations in this gene are associated with Ehlers-Danlos syndrome types IV, and with aortic and arterial aneurysms. (Lee et al., 2008; Jeong et al., 2012) |
| Dna / Rna | The COL3A1 gene, located at chromosome 2q32, contains 51 exons spanning 38.43 kb of genomic distance. Two transcripts, resulting from the use of alternative polyadenylation sites, have been identified for this gene (GeneCards GCID:GC02P189803 (http://www.genecards.org/cgi-bin/carddisp.pl?gene=COL3A1), UniProt P02461-CO3A1_HUMAN (http://www.uniprot.org/uniprot/P02461)). |
| Protein | The gene encodes a protein of 1466 amino acids (aa) (138kDa). The shorter isoform is missing 847-1149 aa. The protein is the pro-alpha1 chains of type III collagen, a fibrillar collagen that is found in extensible connective tissues such as skin, lung, uterus, intestine and the vascular system, and is frequently found in association with type I collagen. The C-terminal propeptide, also known as the COLFI domain, has crucial roles in tissue growth and repair, in which it controls both the intracellular assembly of procollagen molecules and the extracellular assembly of collagen fibrils. It binds a calcium ion which is essential for its function (GeneCards GCID:GC02P189803(http://www.genecards.org/cgi-bin/carddisp.pl?gene=COL3A1), UniProt P02461-CO3A1_HUMAN (http://www.uniprot.org/uniprot/P02461)). |
| Gene Name | PLAG1 (Pleomorphic adenoma gene 1) |
| Location | 8q12.1 |
| Dna / Rna | The gene spans about 50 kb and includes 5 exons. The size of the transcript is about 7 kb. It has two alternative splicing forms (one without exon 2) (GeneCards GCID:GC08M057073 (http://www.genecards.org/cgi-bin/carddisp.pl?gene=PLAG1), UniProt Q6DJT9-PLAG1_HUMAN (http://www.uniprot.org/uniprot/Q6DJT9)). |
| Protein | The gene encodes a 500-aa zinc finger protein (74 kDa) with two putative nuclear localization signals (Kas et al., 1997). When activated, it acts as a transcription factor that up-regulates target genes, such as IGFII, leading to uncontrolled cell proliferation. When overexpressed in cultured cells, it increases the proliferation rate and transformation. Other target genes such as CRLF1, CRABP2, CRIP2, PIGF are strongly induced in cells with PLAG1 induction. PLAG1 is a proto-oncogene whose ectopic expression can trigger the development of lipoblastomas and pleomorphic adenomas of the salivary gland (Hensen et al., 2002; Voz et al., 2004; Zatkova et al., 2004) (GeneCards GCID:GC08M057073 (http://www.genecards.org/cgi-bin/carddisp.pl?gene=PLAG1), UniProt Q6DJT9-PLAG1_HUMAN (http://www.uniprot.org/uniprot/Q6DJT9)). |
6. Result of the chromosomal anomaly
| Hybrid Gene | |
| Note | The fusion occurs as a result of a cryptic, intrachromosomal rearrangement in tumors with apparently normal karyotypes. Comparison of the fusion gene with the wild type reveals that the fusion gene is associated with the t(2;8)(q31;q12.1) translocation. The first exon of COL3A1 is fused to either exon 2 or exon 3 of PLAG1 (Yoshida et al., 2014). |
| Description | PLAG1 has a genomic fusion breakpoint in intron 1 resulting in alternative splicing of exon 2. The start codon of PLAG1 is located in exon 4 (Van Dyck et al., 2007), and the coding sequence of PLAG1 is preserved (Yoshida et al., 2014). This supports the molecular mechanism of overexpression of PLAG1 through promoter swapping: as a result of the translocation, the constitutively active promoter of the partner gene drives the ectopic expression of PLAG1 (Hibbard et al., 2000) |
| Detection | RT-PCR using total RNA extracted from frozen tumor tissue. The COL3A1/PLAG1 fusion transcript was amplified with primers 5'-AGGGGAGCTGGCTACCCTCC-3' (forward), and, 5'-ACGTTTCCCTGAAGGGACTT-3' (reverse). COL3A1/PLAG1-fusion transcripts of 345 bp and 450 bp were detected (Yoshida et al., 2014). |
| Fusion Protein | |
| Note | No fusion protein exist for reasons the above. |
| Expression Localisation | PLAG1 protein localizes to the nucleus (Bahrami et al.,2012). |
7. Bibliography
| PLAG1 alteration in carcinoma ex pleomorphic adenoma: immunohistochemical and fluorescence in situ hybridization studies of 22 cases. |
| Bahrami A, Dalton JD, Shivakumar B, Krane JF |
| Head and Neck Pathology. 2012; 6(3): 328-335 |
| PMID 22485045 |
| The tumorigenic diversity of the three PLAG family members is associated with different DNA binding capacities. |
| Hensen K, Van Valckenborgh IC, Kas K, Van de Ven WJ, Voz ML |
| Cancer Research. 2002; 62(5):1510-1517. |
| PMID 11888928 |
| PLAG1 fusion ongogenesis in lipoblastoma. |
| Hibbard MK, Kozakewich HP, Dal Cin P, Sciot R, Tan X, Xiao S, Fletcher JA |
| Cancer Research. 2000;60(17):4869-4872. |
| PMID 10987300 |
| Lipoblastoma and lipoblastomatosis in infancy and childhood: histopathologic, ultrastructural, and cytogenetic features. |
| Hicks J, Dilley A, Patel D, Barrish J, Zhu SH, Brandt M |
| Ultrastructural pathology. 2001; 25(4):321-333. |
| PMID 11577778 |
| Loss of Col3a1, the gene for Ehlers-Danlos syndrome type IV, results in neocortical dyslamination. |
| Jeong SJ, Li S, Luo R, Strokes N, Piao X |
| PLoS One 7(1): e29767. |
| PMID 22235340 |
| Lipoblastoma in infancy and childhood. |
| Jimenez JF |
| Journal of surgical oncology. 1986; 32(4):238-244. |
| PMID 3736068 |
| Promoter swapping between the genes for a novel zinc finger protein and beta-catenin in pleiomorphic adenomas with t(3;8)(p21;q12) translocations. |
| Kas K, Voz ML, Röijer E, Aström AK, Meyen E, Stenman G, Van de Ven WJ |
| Nature Genetics. 1997; 15(2): 170-174. |
| PMID 9020842 |
| Atypical lipomatous tumor in a 14-year-old patient: distinction from lipoblastoma using FISH analysis. |
| Kuhnen C, Mentzel T, Fisseler-Eckhoff A, Debiec-Rychter M, Sciot R |
| Virchows Archiv. 2002; 441(3): 299-302. |
| PMID 12242528 |
| A novel COL3A1 gene mutation in patient with aortic dissected aneurysm and cervical artery dissections. |
| Lee ST, Kim JA, Jang SY, Kim DK, Kim JW, Ki CS |
| Heart and Vessels. 2008; 23(2): 144-148. |
| PMID 18389341 |
| Surgical management of lipoblastoma. |
| McVay MR, Keller JE, Wagner CW, Jackson RJ, Smith SD |
| Journal of Pediatric surgery. 2006; 41(6):1067-1071. |
| PMID 16769336 |
| Differential diagnosis of lipoma-like lipoblastoma. |
| Morerio C, Nozza P, Tassano E, Rosanda C, Granata C, Conte M, Panarello C |
| Pediatric Blood & Cancer. 2009; 52(1): 132-134. |
| PMID 18798558 |
| PLAG1, the prototype of the PLAG gene family: versatility in tumour development (review). |
| Van Dyck F, Declercq J, Braem CV, Van de Ven WJ |
| International Journal of Oncology. 2007; 30(4): 765-774. |
| PMID 17332914 |
| Microarray screening for target genes of the proto-oncogene PLAG1 |
| Voz ML, Mathys J, Hensen K, Pendeville H, Van Valckenborgh I, Van Huffel C, Chavez M, Van Damme B, De Moor B, Moreau Y, Van de Ven WJ |
| Oncogene. 2004; 23(1):179-191. |
| PMID 14712223 |
| Lipomatous tumors. |
| Weiss SW |
| Monographs in Pathology. 1996; 38 :207-239. |
| PMID 8744279 |
| Identification of COL3A1 and RAB2A as novel translocation partner genes of PLAG1 in lipoblastoma. |
| Yoshida H, Miyachi M, Ouchi K, Kuwahara Y, Tsuchiya K, Iehara T, Konishi E, Yanagisawa A, Hosoi H |
| Genes, chromosomes & cancer. 2014; 53(7):606-611. |
| PMID 24700772 |
| Amplification and overexpression of the IGF2 regulator PLAG1 in hepatoblastoma. |
| Zatkova A, Rouillard JM, Hartmann W, Lamb BJ, Kuick R, Eckart M, von Schweinitz D, Koch A, Fonatsch C, Pietsch T,Hanash SM, Wimmer K |
| Genes, chromosomes & cancer. 2004; 39(2):126-137. |
| PMID 14695992 |
| Lipoblastoma in adolescents and young adults: report of six cases with FISH analysis. |
| de Saint Aubain Somerhausen N, Coindre JM, Debiec-Rychter M, Delplace J, Sciot R |
| Histopathology. 2008; 52(3): 238-244. |
| PMID 18269579 |
8. Citation
| This paper should be referenced as such : |
| Hideki Yoshida, Mitsuru Miyachi, Hajime Hosoi |
| Soft Tissues: Lipoblastoma with t(2;8)(q31;q12.1) COL3A1/PLAG1 |
| Atlas Genet Cytogenet Oncol Haematol. 2015;19(6):414-416. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://atlasgeneticsoncology.usal.es/classic/Tumors/t28q31q12LipoblastID6626.html |
9. Translocations implicated (Data extracted from papers in the Atlas)
10. External links
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed Nov 28 16:26:36 CET 2018 |
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