Bone: Subungual exostosis with t(X;6)(q13;q22) COL4A5/COL12A1

2007-07-01 Clelia Tiziana Storlazzi , Fredrik Mertens Affiliation

1.Department of Genetics, Microbiology, University of Bari, Bari, Italy (CTS); Department of Clinical Genetics, Lund University Hospital, Lund, Sweden (FM)

Classification

Note

Benign bone-producing neoplasm of unknown cellular origin.

Clinics and Pathology

Phenotype stem cell origin

Unknown.

Embryonic origin

Unknown.

Etiology

Unknown.

Epidemiology

Affects children and young adults.

Clinics

Subungual exostosis usually presents as a slowly growing, painful mass localized dorsomedially in the distal phalanx, and in contrast to osteochondroma, there is usually no continuity with the underlying cortex.

Treatment

Surgical excision, but local recurrences are not uncommon.

Prognosis

Excellent.

Cytogenetics

Partial G-banding karyotype showing chromosomes 6 and X in a case of subungual exostosis. The arrows indicate the breakpoints.

Cytogenetics morphological

t(X;6)(q22;q13-14).

Cytogenetics molecular

A Probe specific for COL12A1 (RP11-815E21) identified the breakpoint in 6q14.1, as it showed splitting signals on der(X) and der(6). On the same chromosomes, these signals colocalized with the signals of RP11-815E21, encompassing the COL4A5 and IRS4 genes in band Xq22.3.

FISH experiment revealing the breakpoint regions on both chromosomes 6 and X on a case of subungual exostosis.

Probes

RP11-815E21 (COL4A5 and IRS4); RP11-1072D13 (COL12A1).

Variants

The breakpoint on chromosome 6 could be centromeric to COL4A5, in an unknown location.

Genes Involved and Proteins

Gene name

COL4A5 (collagen type IV alpha 5 chain)

Location

Xq22.3

Note

It is currently unknown whether any of these two genes is involved in the pathogenesis of subungual exostosis.

Dna rna description

Genomic (chrX:107,569,810-107,827,431). Three transcript variants: isoform 1 (NM_000495), isoform 2 (NM_033380), isoform 3 (NM_03338).

Protein description

Three proteins, respectively encoded by the isoform 1 (695 aa), isoform 2 (1691 aa), and isoform 3 (1688 aa).

Gene name

COL12A1 (collagen type XII alpha 1 chain)

Location

6q13

Dna rna description

Genomic (chr6:75,850,762-75,972,343). Two transcript variants, a long (NM_004370) and a short isoform (NM_080645).

Protein description

Two proteins: 1899 amino acids (aa) and 3063 aa, respectively encoded by the short and long transcript isoforms.

Result of the chromosomal anomaly

Note

No detected fusion gene.

To be Noted

Note

To elucidate how the transcription of these genes is affected by the translocation, further fresh or fresh frozen samples need to be studied.

Article Bibliography

Pubmed ID	Last Year	Title	Authors
9885985	1999	Clonal chromosome abnormalities in a so-called Dupuytren's subungual exostosis.	Dal Cin P et al
11712058	2001	Subungual exostosis of the third toe.	Ilyas W et al
10992031	2000	Imaging of osteochondroma: variants and complications with radiologic-pathologic correlation.	Murphey MD et al
16284948	2006	Rearrangement of the COL12A1 and COL4A5 genes in subungual exostosis: molecular cytogenetic delineation of the tumor-specific translocation t(X;6)(q13-14;q22).	Storlazzi CT et al
15252309	2004	Distinct chromosomal rearrangements in subungual (Dupuytren) exostosis and bizarre parosteal osteochondromatous proliferation (Nora lesion).	Zambrano E et al

External Links

Citation

Clelia Tiziana Storlazzi ; Fredrik Mertens

Bone: Subungual exostosis with t(X;6)(q13;q22) COL4A5/COL12A1

Atlas Genet Cytogenet Oncol Haematol. 2007-07-01

Online version: http://atlasgeneticsoncology.org/solid-tumor/5526/case-report-explorer/js/lib/teaching-explorer/