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Rearrangement of chromosome bands 12q14~15 causing HMGA2-SOX5 gene fusion and HMGA2 expression in extraskeletal osteochondroma.

Panagopoulos I, Bjerkehagen B, Gorunova L, Taksdal I, Heim S - Oncol. Rep. (2015)

Bottom Line: We describe two cases of extraskeletal osteochondroma in which chromosome bands 12q14~15 were visibly rearranged through a pericentric inv(12).The observed pattern is similar to rearrangements of HMGA2 found in several other benign mesenchymal tumors, i.e., disruption of the HMGA2 locus leaves intact exons 1-3 which encode the AT-hook domains and separates them from the 3'-terminal part of the gene.Our data therefore show that a subset of soft tissue osteochondromas shares pathogenetic involvement of HMGA2 with lipomas, leiomyomas and other benign connective tissue neoplasms.

View Article: PubMed Central - PubMed

Affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.

ABSTRACT
We describe two cases of extraskeletal osteochondroma in which chromosome bands 12q14~15 were visibly rearranged through a pericentric inv(12). Molecular analysis of the first tumor showed that both transcript 1 (NM_003483) and transcript 2 (NM_003484) of HMGA2 were expressed. In the second tumor, the inv(12) detected by karyotyping had resulted in an HMGA2-SOX5 fusion transcript in which exons 1-3 of HMGA2 were fused with a sequence from intron 1 of SOX5. The observed pattern is similar to rearrangements of HMGA2 found in several other benign mesenchymal tumors, i.e., disruption of the HMGA2 locus leaves intact exons 1-3 which encode the AT-hook domains and separates them from the 3'-terminal part of the gene. Our data therefore show that a subset of soft tissue osteochondromas shares pathogenetic involvement of HMGA2 with lipomas, leiomyomas and other benign connective tissue neoplasms.

No MeSH data available.


Related in: MedlinePlus

Extraskeletal osteochondroma with expression of HMGA2 transcripts 1 and 2. Cytogenetic, FISH and PCR analyses of case 1. (A) Chromosome 12 ideogram with the location of the HMGA2 locus and the location of the BACs used for FISH experiments. The investigated region is shown as a red box on the chromosome 12 ideogram. (B) Partial karyotype showing the chromosome aberrations der(5)t(5;12)(q35;q14~15) and der(12)t(5;12)inv(12)(p11q14~15) together with the corresponding normal chromosomes. Arrows indicate breakpoints. (C) FISH showing that the green signal (pool of the BACs RP118B13, RP11-745O10, and RP11-263A04) is deleted and that the red signal (pool of the BACs RP11-185K16, RP11-30I11, and RP11-662G15) is split and seen on both der(5) and der(12) chromosomes. (D) FISH showing that the probe RP11-182F04 is seen as one copy on normal chromosome 12. (E) FISH showing that the RP11-662G15 is split and seen on der(5), der(12), and normal chromosome 12. (F) 3′-RACE amplified a single cDNA fragment (lane R). (G) Partial sequence chromatogram of the 3′-RACE amplified cDNA fragment showing (arrow) the junction of exon 3 and exon 4 of HMGA2 transcript variant 2 with accession number NM_003484. FISH, fluorescence in situ hybridization.
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f3-or-34-02-0577: Extraskeletal osteochondroma with expression of HMGA2 transcripts 1 and 2. Cytogenetic, FISH and PCR analyses of case 1. (A) Chromosome 12 ideogram with the location of the HMGA2 locus and the location of the BACs used for FISH experiments. The investigated region is shown as a red box on the chromosome 12 ideogram. (B) Partial karyotype showing the chromosome aberrations der(5)t(5;12)(q35;q14~15) and der(12)t(5;12)inv(12)(p11q14~15) together with the corresponding normal chromosomes. Arrows indicate breakpoints. (C) FISH showing that the green signal (pool of the BACs RP118B13, RP11-745O10, and RP11-263A04) is deleted and that the red signal (pool of the BACs RP11-185K16, RP11-30I11, and RP11-662G15) is split and seen on both der(5) and der(12) chromosomes. (D) FISH showing that the probe RP11-182F04 is seen as one copy on normal chromosome 12. (E) FISH showing that the RP11-662G15 is split and seen on der(5), der(12), and normal chromosome 12. (F) 3′-RACE amplified a single cDNA fragment (lane R). (G) Partial sequence chromatogram of the 3′-RACE amplified cDNA fragment showing (arrow) the junction of exon 3 and exon 4 of HMGA2 transcript variant 2 with accession number NM_003484. FISH, fluorescence in situ hybridization.

Mentions: The clones used were RP11-185K16, (chr12:64103524-642 74514), RP11-30I11 (chr12:64178505-64349708), RP11-662 G15 (chr12:64288763-64498219), RP11-182F04 (chr12:644 86880-64635771), RP118B13 (chr12:64644 968-64789255), RP11-745O10 (chr12:64752327-64926193) and RP11-263A04 (chr12:64908453-65103538). All of them are mapped to chromosome band 12q14.3 (Fig. 3A). DNA was extracted and probes were labeled and hybridized according to Abbott Molecular recommendations (http://www.abbottmolecular.com/home.html). Chromosome preparations were counter-stained with 0.2 µg/ml DAPI and overlaid with a 24×50 mm2 coverslip. Fluorescent signals were captured and analyzed using the CytoVision system (Leica Biosystems, Newcastle, UK).


Rearrangement of chromosome bands 12q14~15 causing HMGA2-SOX5 gene fusion and HMGA2 expression in extraskeletal osteochondroma.

Panagopoulos I, Bjerkehagen B, Gorunova L, Taksdal I, Heim S - Oncol. Rep. (2015)

Extraskeletal osteochondroma with expression of HMGA2 transcripts 1 and 2. Cytogenetic, FISH and PCR analyses of case 1. (A) Chromosome 12 ideogram with the location of the HMGA2 locus and the location of the BACs used for FISH experiments. The investigated region is shown as a red box on the chromosome 12 ideogram. (B) Partial karyotype showing the chromosome aberrations der(5)t(5;12)(q35;q14~15) and der(12)t(5;12)inv(12)(p11q14~15) together with the corresponding normal chromosomes. Arrows indicate breakpoints. (C) FISH showing that the green signal (pool of the BACs RP118B13, RP11-745O10, and RP11-263A04) is deleted and that the red signal (pool of the BACs RP11-185K16, RP11-30I11, and RP11-662G15) is split and seen on both der(5) and der(12) chromosomes. (D) FISH showing that the probe RP11-182F04 is seen as one copy on normal chromosome 12. (E) FISH showing that the RP11-662G15 is split and seen on der(5), der(12), and normal chromosome 12. (F) 3′-RACE amplified a single cDNA fragment (lane R). (G) Partial sequence chromatogram of the 3′-RACE amplified cDNA fragment showing (arrow) the junction of exon 3 and exon 4 of HMGA2 transcript variant 2 with accession number NM_003484. FISH, fluorescence in situ hybridization.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4487666&req=5

f3-or-34-02-0577: Extraskeletal osteochondroma with expression of HMGA2 transcripts 1 and 2. Cytogenetic, FISH and PCR analyses of case 1. (A) Chromosome 12 ideogram with the location of the HMGA2 locus and the location of the BACs used for FISH experiments. The investigated region is shown as a red box on the chromosome 12 ideogram. (B) Partial karyotype showing the chromosome aberrations der(5)t(5;12)(q35;q14~15) and der(12)t(5;12)inv(12)(p11q14~15) together with the corresponding normal chromosomes. Arrows indicate breakpoints. (C) FISH showing that the green signal (pool of the BACs RP118B13, RP11-745O10, and RP11-263A04) is deleted and that the red signal (pool of the BACs RP11-185K16, RP11-30I11, and RP11-662G15) is split and seen on both der(5) and der(12) chromosomes. (D) FISH showing that the probe RP11-182F04 is seen as one copy on normal chromosome 12. (E) FISH showing that the RP11-662G15 is split and seen on der(5), der(12), and normal chromosome 12. (F) 3′-RACE amplified a single cDNA fragment (lane R). (G) Partial sequence chromatogram of the 3′-RACE amplified cDNA fragment showing (arrow) the junction of exon 3 and exon 4 of HMGA2 transcript variant 2 with accession number NM_003484. FISH, fluorescence in situ hybridization.
Mentions: The clones used were RP11-185K16, (chr12:64103524-642 74514), RP11-30I11 (chr12:64178505-64349708), RP11-662 G15 (chr12:64288763-64498219), RP11-182F04 (chr12:644 86880-64635771), RP118B13 (chr12:64644 968-64789255), RP11-745O10 (chr12:64752327-64926193) and RP11-263A04 (chr12:64908453-65103538). All of them are mapped to chromosome band 12q14.3 (Fig. 3A). DNA was extracted and probes were labeled and hybridized according to Abbott Molecular recommendations (http://www.abbottmolecular.com/home.html). Chromosome preparations were counter-stained with 0.2 µg/ml DAPI and overlaid with a 24×50 mm2 coverslip. Fluorescent signals were captured and analyzed using the CytoVision system (Leica Biosystems, Newcastle, UK).

Bottom Line: We describe two cases of extraskeletal osteochondroma in which chromosome bands 12q14~15 were visibly rearranged through a pericentric inv(12).The observed pattern is similar to rearrangements of HMGA2 found in several other benign mesenchymal tumors, i.e., disruption of the HMGA2 locus leaves intact exons 1-3 which encode the AT-hook domains and separates them from the 3'-terminal part of the gene.Our data therefore show that a subset of soft tissue osteochondromas shares pathogenetic involvement of HMGA2 with lipomas, leiomyomas and other benign connective tissue neoplasms.

View Article: PubMed Central - PubMed

Affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.

ABSTRACT
We describe two cases of extraskeletal osteochondroma in which chromosome bands 12q14~15 were visibly rearranged through a pericentric inv(12). Molecular analysis of the first tumor showed that both transcript 1 (NM_003483) and transcript 2 (NM_003484) of HMGA2 were expressed. In the second tumor, the inv(12) detected by karyotyping had resulted in an HMGA2-SOX5 fusion transcript in which exons 1-3 of HMGA2 were fused with a sequence from intron 1 of SOX5. The observed pattern is similar to rearrangements of HMGA2 found in several other benign mesenchymal tumors, i.e., disruption of the HMGA2 locus leaves intact exons 1-3 which encode the AT-hook domains and separates them from the 3'-terminal part of the gene. Our data therefore show that a subset of soft tissue osteochondromas shares pathogenetic involvement of HMGA2 with lipomas, leiomyomas and other benign connective tissue neoplasms.

No MeSH data available.


Related in: MedlinePlus