Dataset Information

DNA copy number alterations in pleomorphic leiomyosarcoma: A case report.

ABSTRACT: Pleomorphic leiomyosarcoma (P-LMS) is a rare morphological variant of LMS. The current study presents the cytogenetic data of a P-LMS that arose in the axillary region of a 31-year-old male. The results of array-based comparative genomic hybridization for the primary tumor showed DNA copy number alteration (DCNA) gains of 8ptel, 17ptel and 17q11.2 and losses of 2ptel, 7ptel, 7qtel, 10p15, 12p12-13.1, 13q14.2-14.3, 15q25-26 and Yq11. However, a metastatic lesion showed cytogenetic data different from the primary tumor DCNAs, with only the locus of 17ptel (282M15/SP6) in common between them. These observations add to the spectrum of DCNAs that have been reported in previous cases of LMS and provide novel cytogenetic data.

SUBMITTER: Kanamori M

PROVIDER: S-EPMC4049769 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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DNA copy number alterations in pleomorphic leiomyosarcoma: A case report.

Kanamori Masahiko M Yasuda Taketoshi T Nogami Shigeharu S Suzuki Kayo K Hori Takeshi T

Oncology letters 20140403 6

Pleomorphic leiomyosarcoma (P-LMS) is a rare morphological variant of LMS. The current study presents the cytogenetic data of a P-LMS that arose in the axillary region of a 31-year-old male. The results of array-based comparative genomic hybridization for the primary tumor showed DNA copy number alteration (DCNA) gains of 8ptel, 17ptel and 17q11.2 and losses of 2ptel, 7ptel, 7qtel, 10p15, 12p12-13.1, 13q14.2-14.3, 15q25-26 and Yq11. However, a metastatic lesion showed cytogenetic data different ...[more]

PMID: 24932246

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Project description:Pleomorphic xanthoastrocytoma (PXA) is a rare localized glioma characterized by frequent BRAF V600E mutation and CDKN2A/B deletion. We explored the association of copy-number variants (CNVs) with BRAF mutations, tumor grade, and patient survival in a cohort of 41 PXA patients using OncoScan chromosomal microarray. Primary resection specimens were available in 38 cases, including 24 PXA and 14 anaplastic PXA (A-PXA), 23 BRAF V600E mutant tumors (61%). CNVs were identified in all cases and most frequently involved chromosome 9 with homozygous CDKN2A/B deletion (n = 33, 87%), a higher proportion than previously detected by comparative genomic hybridization (50%-60%) (37). CDKN2A/B deletion was present in similar proportion of PXA (83%), A-PXA (93%), BRAF V600E (87%), and wild-type (87%) tumors. Whole chromosome gains/losses were frequent, including gains +7 (n = 15), +2 (n = 11), +5 (n = 10), +21 (n = 10), +20 (n = 9), +12 (n = 8), +15 (n = 8), and losses -22 (n = 11), -14 (n = 7), -13 (n = 5). Losses and copy-neutral loss of heterozygosity were significantly more common in A-PXA, involving chromosomes 22 (P = 0.009) and 14 (P = 0.03). Amplification of 8p and 12q was identified in a single tumor. Histologic grade was a robust predictor of overall survival (P = 0.003), while other copy-number changes, including CDKN2A/B deletion, did not show significant association with survival. Distinct histologic patterns of anaplasia included increased mitotic activity in an otherwise classic PXA or associated with small cell, fibrillary, or epithelioid morphology, with loss of SMARCB1 expression in one case. In 10 cases, matched specimens were compared, including A-PXA with areas of distinct low- and high-grade morphology (n = 2), matched primary/tumor recurrence (n = 7), or both (n = 1). Copy-number changes on recurrence/anaplastic transformation were complex and highly variable, from nearly identical profiles to numerous copy-number changes. Overall, we confirm CDKN2A/B deletion as key a feature of PXA not associated with tumor grade or BRAF mutation, but central to the underlying genetics of PXA.

Project description:Soft tissue sarcomas (STS) often present a significant diagnostic challenge as many STS bear histologic resemblance, but are known to have very different clinical and biologic characteristics. Some STS subtypes are characterized by specific genetic abnormalities and this has helped in their classification, diagnosis and even treatment. However, a large majority of STS have no known specific genetic aberrations even though they almost always have highly aberrant karyotypes. We therefore hypothesize that the latter subgroup of STS bear genetic abnormalities that are sub-type specific, but as yet unidentified. High-resolution mapping of copy number aberrations in cancer genomes is a valuable way of identifying recurrent genomic changes that could be of pathogenetic significance. Traditionally, this has been done using high quality DNA obtained from fresh frozen tissue or cells and archived tissue is generally regarded as unsuitable because of the degradative effects of formalin fixation on DNA. Utility of archival tumour material for such molecular genetic analysis is vital, especially for rare cancers like STS but recent efforts to accomplish this have produced variable results. We therefore set out, in addition to optimize a protocol for obtaining genomic copy number data from formalin-fixed, paraffin-embedded (FFPE) STS material that is comparable to that from fresh frozen (FF) material. Microarray-based Comparative Genomic Hybridization (aCGH), a high- resolution, genome-wide method was used to identify somatic copy number aberrations (SCNAs) in primary STS samples (fresh frozen and archival FFPE), using an optimized protocol for labeling DNA. Findings were confirmed using Conventional Cytogenetics and Fluorescence in-situ Hybridization (FISH). Data obtained from paired samples (FF and FFPE) of the same tumours showed similar results and array results were consistently of good quality. On-going analysis of the recurrent SCNAs in combination with expression data and clinical correlates may serve to identify specific patterns that can serve as diagnostic markers, characterize subgroups with prognostic implication or identify potential therapeutic targets.

Dataset Information

DNA copy number alterations in pleomorphic leiomyosarcoma: A case report.

Publications

DNA copy number alterations in pleomorphic leiomyosarcoma: A case report.

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