Molecular cytogenetic characterization of chromosome aberrations in soft tissue and bone tumors

Malin A Nilsson

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)


Bone and soft tissue tumors (BSTT) belong to a diverse group of solid tumors of mesenchymal origin, with a large number of histological types affecting individuals of all ages. The general aim of the present thesis (Articles I-V) was to investigate in detail the genetic aberrations in selected subtypes of benign and malignant BSTT. Aberrations identified by chromosome banding analysis were studied in more detail by molecular techniques, in particular by FISH. I: The results demonstrate that the frequent chromosome 1 breakpoints in tenosynovial giant cell tumors are clustered to a common region in chromosome subband 1p13.2, indicating that this segment contains a gene that through dysregulation or formation of a fusion gene plays a role in the tumorigenesis. Chromosome 2 was the most frequent translocation partner. The breakpoints in 2q35-37 were less clustered than the chromosome 1 breakpoints, but were at least in four cases localized together in a sequence where the G protein-coupled receptor gene CMKOR1 is located. II: The finding of t(1;17)(q32;q21) as a characteristic, recurrent and probably pathogenetically significant aberration in bizarre parosteal osteochondromatous proliferation (Nora's lesion) indicate that it is a tumour disease. III: The candidate oncogenes COAS1-3 were amplified in 56 % of 48 BSTTs analyzed. Medium and high-level amplification was primarily seen among lipomatous tumors, where the extra copies were localized preferentially in ring and giant marker chromosomes, often together with amplified MDM2. IV: A new variant type of structural aberration was described in an atypical lipomatous tumor. Intermixed sequences from chromosomes 8 and 12 resulted in extra copies of MDM2 and HMGA2, including a truncated version of the latter. V: Eight lipomas with rearrangements of chromosome bands 12q14-15 and 5q32-33 were analysed by FISH. Five of the cases had a breakpoint in the 5´ part of the early B-cell factor gene (EBF) located at 5q33. On chromosome 12, the breakpoints clustered to the region of the HMGA2 gene. Two new fusion genes, HMGA2/EBF and EBF/BC058822, were identified. In a case with HMGA2/EBF, two splicing variants, one in frame and the other out of frame, were identified.
Tilldelande institution
  • Avdelningen för klinisk genetik
  • Mandahl, Nils, handledare
Tilldelningsdatum2005 feb. 18
ISBN (tryckt)91-85439-04-5
StatusPublished - 2005

Bibliografisk information

Defence details

Date: 2005-02-18
Time: 10:00
Place: Föreläsningssal 3, Centralblocket, Universitetssjukhuset, Lund

External reviewer(s)

Name: Limon, Janusz
Title: Professor
Affiliation: Department of Biology and Genetics, Medical University of Gdánsk, Polen


<div class="article_info">M Nilsson, M Höglund, I Panagopoulos, R Sciot, P Dal Cin, M Debiec-Rychter, F Mertens and N Mandahl. <span class="article_issue_date">2002</span>. <span class="article_title">Molecular cytogenetic mapping of recurrent chromosomal breakpoints in tenosynovial giant cell tumors.</span> <span class="journal_series_title">Virchows Arch</span>, <span class="journal_volume">vol 441</span> <span class="journal_pages">pp 475-80</span>.</div>
<div class="article_info">M Nilsson, HA Domanski, F Mertens and N Mandahl. <span class="article_issue_date">2004</span>. <span class="article_title">Molecular cytogenetic characterization of recurrent translocation breakpoints in bizarre parosteal osteochondromatous proliferation (Nora’s lesion).</span> <span class="journal_series_title">Hum Pathol</span>, <span class="journal_volume">vol 35</span> <span class="journal_pages">pp 1063-9</span>.</div>
<div class="article_info">M Nilsson, LA Meza-Zepeda, F Mertens, A Forus, O Myklebost and N Mandahl. <span class="article_issue_date">2004</span>. <span class="article_title">Amplification of chromosome 1 sequences in lipomatous tumors and other sarcomas.</span> <span class="journal_series_title">Int J Cancer</span>, <span class="journal_volume">vol 109</span> <span class="journal_pages">pp 363-9</span>.</div>
<div class="article_info">M Nilsson, H Domanski, F Mertens and N Mandahl. <span class="article_issue_date">2004</span>. <span class="article_title">Atypical lipomatous tumor with rare structural rearrangements involving chromosomes 8 and 12.</span> <span class="journal_series_title">Oncol Rep</span>, (inpress)</div>
<div class="article_info">M Nilsson, F Mertens, M Höglund, N Mandahl and I Panagopoulos. <span class="article_issue_date">2004</span>. <span class="article_title">Truncation and fusion of HMGA2 in lipomas with complex structural rearrangements of 5q32-33 and 12q14-15.</span> <span class="journal_series_title">Neoplasia</span>, (submitted)</div>

Ämnesklassifikation (UKÄ)

  • Medicinsk genetik


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