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Soft Tissues: Lipoblastoma with t(8;8)(q12;q12) RAB2A/PLAG1

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:

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Abstract Review on lipoblastoma with t(8;8)(q12;q12) RAB2A /PLAG1, with data on clinics, and the genes involved.


Atlas_Id 6627
Phylum Soft Tissues::Lipoblastoma
WHO/OMS Classification Soft Tissues

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).



Genes involved and Proteins

Gene NameRAB2A (RAB2A, member RAS oncogene family)
Location 8q12.1
Dna / Rna The RAB2A gene contains 8 exons spanning 106 kbp of genomic distance that was mapped to chromosome 8q12.1. It has two alternative splicing forms (one without exon 2) as a result of the use of alternative polyadenylation sites (GeneCards CID:GC08P061429 (, UniProt P61019-RAB2A_HUMAN(
Protein The gene encodes a protein of 212 amino acids (23 kDa). The shorter isoform is missing 847-1149 aa. The protein is a member of the Rab family, whose members are small molecular weight guanosine triphosphatases (GTPases) that contain highly conserved domains involved in GTP binding and hydrolysis. The Rabs are membrane-bound proteins, involved in vesicular fusion and trafficking (Ali et al., 2004; Mountjoy et al., 2008). RAB2a is a pre-Golgi intermediate and transports proteins from the endoplasmic reticulum (ER) to the Golgi complex (Tisdale EJ et al., 1996) (GeneCards CID:GC08P061429 (, UniProt P61019-RAB2A_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 (

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 t(8;8)(q12.1;q12.1) translocation. The first exon of RAB2A 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 RAB2A/PLAG1 fusion transcript was amplified with primers 5' CTTCCTCACAGCCCCTCACT-3' (forward), and, 5'- GGAACTGCCCAACTCCACTA-3'(reverse). RAB2A/PLAG1-fusion transcripts of 485 bp and 590 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).


Multiple regions contribute to membrane targeting of Rab GTPases.
Ali BR, Wasmeier C, Lamoreux L, Strom M, Seabra MC
J Cell Sci. 2004; 117: 6401-6412.
PMID 15561774
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
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
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
GTP-binding mutants of rab1 and rab2 are potent inhibitors of vesicular transport from the endoplasmic reticulum to the Golgi complex.
Tisdale EJ, Bourne JR, Khosravi-Far R, Der CJ, Balch WE
J Cell Biol. 1992; 119(4):749-761.
PMID 1429835
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


This paper should be referenced as such :
Hideki Yoshida, Mitsuru Miyachi, Hajime Hosoi
Soft Tissues: Lipoblastoma with t(8;8)(q12;q12) RAB2A/PLAG1
Atlas Genet Cytogenet Oncol Haematol. 2015;19(7):481-483.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Translocations implicated (Data extracted from papers in the Atlas)

 t(8;8)(q12;q12) RAB2A/PLAG1

External links

Mitelman database t(8;8)(q12;q12) [CaseList]     t(8;8)(q12;q12) [Transloc - MCList]   RAB2A/PLAG1 Fusion - MCList]
arrayMap arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
Disease databaseSoft Tissues: Lipoblastoma with t(8;8)(q12;q12) RAB2A/PLAG1
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed

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