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| 2. |
- Bartuma, Hammurabi, et al.
(författare)
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Assessment of the clinical and molecular impact of different cytogenetic subgroups in a series of 272 lipomas with abnormal karyotype
- 2007
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 46:6, s. 594-606
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Tidskriftsartikel (refereegranskat)abstract
- Conventional lipomas harbor karyotypic changes that could be subdivided into four, usually mutually exclusive, categories: rearrangement, in particular through translocations, of chromosome bands 12q13-15, resulting in deregulation of the HMGA2 gene, loss of material from or rearrangement of chromosome 13, supernumerary ring or giant marker chromosomes, and aberrations of chromosome band 6p21. In the present study, 272 conventional lipomas, two-thirds of them deep-seated, with acquired clonal chromosome changes were assessed with regard to karyotypic and clinical features. A nonrandom distribution of breakpoints and imbalances could be confirmed, with 83% of the cases harboring one or more of the previously known cytogenetic hallmarks. Correlation with clinical features revealed that lipomas with rings/giant markers were larger, occurred in older patients, were more often deep-seated, and seemed to have an increased tendency to recur locally, compared with tumors with other chromosome aberrations. The possible involvement of the HMGA2 gene in cases that did not show any of the characteristic cytogenetic changes was further evaluated by locus-specific metaphase fluorescence in situ hybridization (FISH) and RT-PCR, revealing infrequent cryptic disruption of the gene but abundant expression of full length or truncated transcripts. By FISH, we could also show that breakpoints in bands 10q22-23 do not affect the MYST4 gene, whereas breakpoints in 6p21 or 8q11-12 occasionally target the HMGA1 or PLAG1 genes, respectively, also in conventional lipomas.
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| 3. |
- Bartuma, Hammurabi, et al.
(författare)
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Cytogenetic and molecular cytogenetic findings in lipoblastoma.
- 2008
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Ingår i: Cancer Genetics and Cytogenetics. - : Elsevier BV. - 0165-4608. ; 183:1, s. 60-63
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Tidskriftsartikel (refereegranskat)abstract
- Lipoblastoma is a rare benign tumor that arises from embryonic adipose tissue and usually occurs in young children. Here, we present a review of available cytogenetic data and the karyotypes of 10 new cases of lipoblastoma, of which 7 could be studied further by fluorescence in situ hybridization (FISH) with regard to the involvement of the PLAG1 gene. All seven tumors with clonal aberrations harbored breakpoints in 8q11 approximately q13, in agreement with literature data. Including previously published cases, 33/40 (82%) lipoblastomas had rearrangement of the 8q11 approximately q13 region. These rearrangements target the PLAG1 gene, which becomes upregulated through promoter swapping. FISH revealed that five of seven cases in our series had a rearrangement of the PLAG1 gene. Occasionally, there can be difficulties in distinguishing a lipoblastoma from a conventional lipoma or a myxoid liposarcoma. As 8q11 approximately q13 rearrangements have been reported in only 3% of conventional lipomas and never in myxoid liposarcoma, cytogenetic analysis or FISH for the PLAG1 gene can provide useful differential diagnostic information.
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| 4. |
- Bartuma, Hammurabi, et al.
(författare)
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Expression levels of HMGA2 in adipocytic tumors correlate with morphologic and cytogenetic subgroups.
- 2009
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Ingår i: Molecular Cancer. - : Springer Science and Business Media LLC. - 1476-4598. ; 8:Jun 9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The HMGA2 gene encodes a protein that alters chromatin structure. Deregulation, typically through chromosomal rearrangements, of HMGA2 has an important role in the development of several mesenchymal neoplasms. These rearrangements result in the expression of a truncated protein lacking the acidic C-terminus, a fusion protein consisting of the AT-hook domains encoded by exons 1-3 and parts from another gene, or a full-length protein; loss of binding sites for regulatory microRNA molecules from the 3' untranslated region (UTR) of HMGA2 has been suggested to be a common denominator. METHODS: Seventy adipocytic tumors, representing different morphologic and cytogenetic subgroups, were analyzed by qRT-PCR to study the expression status of HMGA2; 18 of these tumors were further examined by PCR to search for mutations or deletions in the 3'UTR. RESULTS: Type (full-length or truncated) and level of expression varied with morphology and karyotype, with the highest levels in atypical lipomatous tumors and lipomas with rearrangements of 12q13-15 and the lowest in lipomas with 6p- or 13q-rearrangements, hibernomas, spindle cell lipomas and myxoid liposarcomas. All 18 examined tumors showed reduced or absent expression of the entire, or parts of, the 3'UTR, which was not due to mutations at the DNA level. CONCLUSION: In adipocytic tumors with deregulated HMGA2 expression, the 3'UTR is consistently lost, either due to physical disruption of HMGA2 or a shift to production of shorter 3'UTR.
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| 5. |
- Bartuma, Hammurabi, et al.
(författare)
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Fusion of the FUS and CREB3L2 genes in a supernumerary ring chromosome in low-grade fibromyxoid sarcoma.
- 2010
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Ingår i: Cancer Genetics and Cytogenetics. - : Elsevier BV. - 0165-4608. ; 199:2, s. 143-146
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Tidskriftsartikel (refereegranskat)abstract
- Low-grade fibromyxoid sarcoma (LGFMS) is a rare, low-grade malignant soft tissue tumor that is often mistaken for either benign or more malignant tumor types. Commonly, this tumor affects young adults and typically arises in the deep proximal extremities or trunk with frequent recurrences and can metastasize to the lungs many years later. Most cases have a recurrent balanced translocation involving chromosomes 7 and 16, t(7;16)(q32-34;p11), which leads to the fusion of the FUS and CREB3L2 genes. However, supernumerary ring chromosomes have been identified in a subset of FUS/CREB3L2-positive LGFMS, but it has not yet been formally demonstrated that such ring chromosomes harbor the FUS/CREB3L2 fusion gene. Here, we report the genetic findings of a supernumerary ring chromosome from an LGFMS from a 77-year-old man. Chromosome banding analysis revealed a supernumerary ring chromosome, and further studies with fluorescence in situ hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR) showed that the ring contained material from chromosomes 7 and 16, that the FUS gene was present in two rearranged copies, and that it expressed the FUS/CREB3L2 fusion gene. Moreover, an assessment of previously reported cases showed that tumors with ring chromosomes relapsed more often than tumors with a balanced t(7;16), suggesting that ring formation in LGFMS is correlated with tumor progression.
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| 6. |
- Bartuma, Hammurabi, et al.
(författare)
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Gene expression and single nucleotide polymorphism array analyses of spindle cell lipomas and conventional lipomas with 13q14 deletion.
- 2011
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 50, s. 619-632
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Tidskriftsartikel (refereegranskat)abstract
- Spindle cell lipomas (SCL) are circumscribed, usually s.c. tumors that typically occur on the posterior neck, shoulder, and back of middle aged men. Cytogenetically, almost all SCL are characterized by deletions of chromosome arm 13q, often in combination with loss of 16q. Deletions of 13q are seen also in approximately 15% of conventional lipomas. Through single nucleotide polymorphism (SNP) array analyses, we identified two minimal deleted regions (MDR) in 13q14 in SCL. In MDR1, four genes were located, including the tumor suppressor gene RB1. MDR1 in SCL overlapped with the MDR detected in conventional lipomas with 13q14 deletion. In MDR2 in SCL there were 34 genes and the two microRNA (miRNA) genes miR-15a and miR-16-1. Global gene expression analysis was used to study the impact of the deletions on genes mapping to the two SCL-associated MDR. Five genes (C13orf1, DHRS12, ATP7B, ALG11, and VPS36) in SCL and one gene (C13orf1) in conventional lipomas with 13q-deletions were found to be significantly underexpressed compared with control tissues. Quantitative real-time PCR showed that miR-16-1 was expressed at lower levels in SCL than in the control samples. No mutations were found at sequencing of RB1, miR-15a, and miR-16-1. Our findings further delineate the target region for the 13q deletion in SCL and conventional lipomas and show that the deletions are associated with down-regulated expression of several genes, notably C13orf1, which was the only gene to be significantly down-regulated in both tumor types. © 2011 Wiley-Liss, Inc.
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| 7. |
- Billing, V, et al.
(författare)
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Deep-seated ordinary and atypical lipomas - Histopathology, cytogenetics, clinical features, and outcome in 215 tumours of the extremity and trunk wall
- 2008
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Ingår i: Journal of Bone and Joint Surgery: British Volume. - 2044-5377. ; 90B:7, s. 929-933
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Tidskriftsartikel (refereegranskat)abstract
- Deep-seated lipomas are often atypical histologically and are considered by some to have a high risk of recurrence after excision. We reviewed 215 deep-seated lipomas of the extremities and trunk wall with reference to histology, cytogenetics, clinical features and local recurrence. We classified tumours with atypical features and/or ring chromosomes as atypical lipomas. These were more common in men, larger than ordinary lipomas and more often located in the upper leg. The annual incidence was estimated as ten per million inhabitants and the ratio of atypical to ordinary lipomas was 1:3. In total, six tumours (3%), recurred locally after a median of eight years (1 to 16); of these, four were classified as atypical. The low recurrence rate of deep-seated lipomas of the extremity or trunk wall, irrespective of histological subtype, implies that if surgery is indicated, the tumour may be shelled out, that atypical lipomas in these locations do not deserve the designation well-differentiated liposarcoma, and that routine review after surgery is not required.
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| 8. |
- Brekke, Helge R., et al.
(författare)
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Identification of p53 as a strong predictor of survival for patients with malignant peripheral nerve sheath tumors
- 2009
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Ingår i: Neuro-Oncology. - : Oxford University Press (OUP). - 1523-5866 .- 1522-8517. ; 11:5, s. 514-528
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to identify new prognostic biomarkers with clinical impact in malignant peripheral nerve sheath tumor (MPNST), a highly aggressive malignancy for which no consensus therapy exists besides surgery. We have used tissue microarrays (TMAs) to assess in situ expression of 14 cell-cycle-regulating proteins in 64 well-characterized MPNST patients: 36 sporadic and 28 with neurofibromatosis type 1 (NF1). We developed a new software application for evaluation and logistics of the TMA images and performed a literature survey of cell cycle proteins in MPNST. For NF1-associated patients, there was a clear association between nuclear expression of p53 and poor survival (p = 0.004). Among the other proteins analyzed, we also found significant associations between survival and clinical variables, but none were as strong as that for p53. For the total series of MPNSTs, p53 was shown to be an independent predictor of survival, and patients without remission, with tumor size larger than 8 cm, and with positive p53 expression had a 60 times greater risk of dying within the first 5 years compared with the remaining patients (p = 0.000002). This is the most comprehensive study of in situ protein expression in MPNST so far, and expressed p53 was found to be a strong surrogate marker for outcome. Patients in complete remission with a primary p53-positive MPNST diagnosis may be considered in a high-risk subgroup and candidates for adjuvant treatment. Neuro-Oncology 11, 514-528, 2009 (Posted to Neuro-Oncology [serial online], Doc. D08-00271, January 30, 2009.)
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| 9. |
- Dahlén, Anna, et al.
(författare)
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Clustering of deletions on chromosome 13 in benign and low-malignant lipomatous tumors
- 2003
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 103:5, s. 616-623
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Tidskriftsartikel (refereegranskat)abstract
- Deletions and structural rearrangements of the long arm of chromosome 13 are frequently observed in benign and low-malignant lipomatous tumors, but nothing is known about their molecular genetic consequences. We assessed the karyotypes of 40 new and 22 previously published cases (35 ordinary lipomas, 15 spindle cell/pleomorphic lipomas, 2 myxolipomas, 1 angiomyxolipoma and 9 atypical lipomatous tumors) with chromosome 13-abnormalities, and found bands 13q12-22 to be frequently affected. Twenty-seven cases with structural abnormalities within this region were selected for breakpoint and deletion mapping by metaphase fluorescence in situ hybridization (FISH), using a set of 20 probes. Deletions were found in 23 of 27 cases. The remaining 4 cases had seemingly balanced rearrangements. The breakpoints were scattered but clustered to band 13q14, and in all cases with unbalanced abnormalities, a limited region within band 13q14 was partially or completely deleted. A deletion within band 13q14 was found together with a breakpoint on the other homologue in 5 cases, 4 of which could be tested further with regard to the status of the retinoblastoma (RB1)-gene. In all 4 cases, only 1 copy of the gene was deleted. In addition to the breaks and deletions in the vicinity of the RB1-locus, several other regions of 13q were recurrently affected, e.g., in the vicinity of the hereditary breast cancer (BRCA2; 13q12)- and lipoma HMGIC fusion partner (LHFP; 13q13)- genes. Our findings strongly indicate that deletion of a limited region (approximately 2.5 Mbp) within 13q14, distal to the RB1-locus, is of importance in the development of a subset of lipomatous tumors.
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| 10. |
- Domanski, Henryk A, et al.
(författare)
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Core-needle biopsy performed by the cytopathologist : a technique to complement fine-needle aspiration of soft tissue and bone lesions
- 2005
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Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 105:4, s. 229-239
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Fine-needle aspiration cytology (FNAC) is gaining increased popularity in the diagnosis of musculoskeletal lesions; and, in many patients, a definitive diagnosis can be rendered from aspiration smears alone. The main limitation of FNAC of soft tissue and bone neoplasms is in the evaluation of tissue architecture. In addition cytologic specimens are not always adequate for ancillary studies.METHODS: A consecutive series of 130 patients with soft tissue and bone lesions was examined by core-needle biopsy (CNB) performed by a cytopathologist in conjunction with FNAC. The findings of this combined diagnostic approach were compared with histologic diagnoses made on surgical biopsies and resected specimens from 86 patients. Adequate follow-up was available in all patients.RESULTS: FNAC combined with CNB correctly could identify 77 of 78 malignant lesions and 50 of 52 benign lesions. Only seven patients underwent incisional biopsy. The tumor subtype was determined correctly in 30 of 39 patients (77%) and the malignancy grade was determined in 35 of 39 patients (90%) with primary soft tissue and bone sarcomas compared with the biopsy or operative specimens.CONCLUSIONS: FNAC of musculoskeletal tumors/lesions complemented with CNB combined cytomorphology with tissue architecture and ancillary procedures. In the current study, obtaining FNAC as well as CNB at the same clinic visit and by the cytopathologist made preliminary diagnosis on the day of referral possible. This speeded diagnosis increased the number of correct diagnoses and usually enabled correct subtyping and malignancy grading of sarcomas.
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