Soft Tissues: Lipoblastoma with t(2;8)(q32;q12.1) COL3A1/PLAG1

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA
Written2014-10Hideki 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:

(Note : for Links provided by Atlas : click)

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 is a rapidly growing, benign neoplasm. It is a mesenchymal tumor of fetal white fat tissue that appears most commonly in children under three years of age and affects males three times more often than females (McVay et al., 2006). It can present anywhere in the body, but is most commonly seen in the trunk and extremities. Surgical excision is usually curative, with a recurrence rate of about 20% (Jimenez, 1986; Hicks et al., 2001). Histologically, lipoblastoma shows a characteristic lobular architecture, with lobules containing lipoblasts embedded in a myxoid matrix, whereas lipoma is a tumor composed of only mature fat without lobulation (Weiss, 1996; Kuhnen et al., 2002; de Saint Aubain Somerhausen et al., 2008; Morerio et al., 2009).

4. Cytogenetics

t(2;8)(q32;q12) G- banding: - Courtesy Galina Aldrete and Charles D. Bangs
PLAG1 FISH of formalin-fixed paraffin-embedded section showing PLAG1 rearrangement: - Courtesy Gail Aldrete and Charles D. Bangs

5. Genes involved and Proteins

Gene NameCOL3A1 (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 (, UniProt P02461-CO3A1_HUMAN (
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(, UniProt P02461-CO3A1_HUMAN (

Gene NamePLAG1 (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 (, UniProt Q6DJT9-PLAG1_HUMAN (
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 (, UniProt Q6DJT9-PLAG1_HUMAN (

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 :

9. Translocations implicated (Data extracted from papers in the Atlas)

 t(2;8)(q32;q12.1) COL3A1/PLAG1

10. External links

Mitelman database t(2;8)(q32;q12.1) [CaseList]     t(2;8)(q32;q12.1) [Transloc - MCList]   COL3A1/PLAG1 Fusion - MCList]
COSMIC[ COL3A1 ]   [ PLAG1 ]
arrayMap arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
Mitelman databaseCOL3A1/PLAG1[MCList]    COL3A1 (2q32.2) PLAG1 (8q12.1)   t(2;8)(q32;q12)
Disease databaseSoft Tissues: Lipoblastoma with t(2;8)(q32;q12.1) COL3A1/PLAG1
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Nov 28 16:26:36 CET 2018

For comments and suggestions or contributions, please contact us