Cytogenetic analysis of a primary bone angiosarcoma

Dunlap, Jennifer; Magenis, R. Ellen; Davis, Craig B.; Himoe, Eleanor; Mansoor, Atiya

doi:10.1016/j.cancergencyto.2009.04.008

Cited by 21 publications

(9 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We have identified a number of somatic copy number events, mostly marked by amplifications, and SNV alterations in this patient’s tumor. Our approach did not uncover any translocations that could result in oncogenic fusions previously reported in primary angiosarcomas [48, 49]. Copy number coupled with the translocation analysis suggested a presence of a circular chromosome harboring the MDM4 gene.…”

Section: Discussionmentioning

confidence: 71%

Case report: whole exome sequencing of primary cardiac angiosarcoma highlights potential for targeted therapies

et al. 2017

View full text Add to dashboard Cite

BackgroundPrimary cardiac angiosarcomas are rare, but they are the most aggressive type of primary cardiac neoplasms. When patients do present, it is with advanced pulmonary and/or cardiac symptoms. Therefore, many times the correct diagnosis is not made at the time of initial presentation. These patients have metastatic disease and the vast majority of these patients die within a few months after diagnosis. Currently the treatment choices are limited and there are no targeted therapies available.Case presentationA 56-year-old male presented with shortness of breath, night sweats, and productive cough for a month. Workup revealed pericardial effusion and multiple bilateral pulmonary nodules suspicious for metastatic disease. Transthoracic echocardiogram showed a large pericardial effusion and a large mass in the base of the right atrium. Results of biopsy of bilateral lung nodules established a diagnosis of primary cardiac angiosarcoma. Aggressive pulmonary disease caused rapid deterioration; the patient went on hospice and subsequently died. Whole exome sequencing of the patient’s postmortem tumor revealed a novel KDR (G681R) mutation, and focal high-level amplification at chromosome 1q encompassing MDM4, a negative regulator of TP53.ConclusionMutations in KDR have been reported previously in angiosarcomas. Previous studies also demonstrated that KDR mutants with constitutive KDR activation could be inhibited with specific KDR inhibitors in vitro. Thus, patients harboring activating KDR mutations could be candidates for treatment with KDR-specific inhibitors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-3000-z) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 71%

Case report: whole exome sequencing of primary cardiac angiosarcoma highlights potential for targeted therapies

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Moreover, in contrast with EH, AS is characterized by infiltrative growth, with irregular anastomosing vascular channels, which are not present in EH 1-3, 9, 34 . This diagnostic challenge is further illustrated by the couple of reported cases in the cytogenetic literature, documenting 14q24.3 locus abnormalities (corresponding to the FOS gene locus), which are most likely in keeping with a cellular/atypical EH rather than either EHE or AS 16, 35 . Based on such a previously reported case with t(10;14)(p13;q24) karyotype 16 , we identified a novel VIM-FOS fusion in two intraosseous cellular EH cases by FISH positional cloning.…”

Section: Discussionmentioning

confidence: 99%

Frequent FOS Gene Rearrangements in Epithelioid Hemangioma

Huang¹,

Zhang

Sung

et al. 2015

American Journal of Surgical Pathology

153

View full text Add to dashboard Cite

Epithelioid hemangioma (EH) is a unique benign vasoformative tumor composed of epithelioid endothelial cells. Although a small subset of EHs with atypical features harbor ZFP36-FOSB fusions, no additional genetic abnormalities have been found to date in the remaining cases. Based on a novel FOS-LMNA gene fusion identified by RNA sequencing in an index case of a skeletal EH with typical morphology, we sought to investigate the prevalence of FOS rearrangement in a large cohort of EHs. Thus 57 additional EH cases lacking FOSB rearrangements were studied for FOS gene abnormalities by FISH and results were correlated with morphologic appearance and clinical presentation. The EHs were subclassified as typical (n=25), cellular (n=21) and ALHE (angiolymphoid hyperplasia with eosinophilia)(n=12) variants. The ALHE was defined as an EH with a vascular ‘blow-out’ pattern associated with a variable degree of inflammation. There were 17 (29%) cases bearing FOS gene rearrangements among 58 cases tested, including 12 males and 5 females, with a mean age of 42 years. Most FOS-rearranged EHs occurred in the bone (10) and soft tissue (6), while only one case was cutaneous. The predominant anatomic site was the extremity (12), followed by trunk (3), head and neck (1), and penis (1). The incidence of FOS rearrangement was significantly higher in bone (59%, p = 0.006) and lower in head and neck (5%, p = 0.009). Twelve of the FOS rearranged cases were cellular EH (p = 0.001) associated with moderate mitotic activity (2-5/10 HPF) and milder inflammatory background. All 12 ALHE cases lacked FOS gene abnormalities, suggesting different pathogenesis. In conclusion, FOS rearrangement was present in a third of EHs across different locations and histologic variants; however, it was more prevalent in cellular EH and intra-osseous lesions, compared to those in skin, soft tissue and head and neck. This genetic abnormality can be useful in challenging cases, to distinguish cellular EHs from malignant epithelioid vascular tumors. These results also suggest that dysregulation of the FOS family of transcription factors through chromosomal translocation is as a key event in the tumorigenesis of EH except for the ALHE variant.

show abstract

“…To date, only a few vascular tumors have been analyzed cytogenetically, with different chromosomal translocations being reported (Boudousquie et al, 1996; He et al, 2006; Dunlap et al, 2009). In 2001, Mendlick et al found an identical chromosomal translocation, t(1;3)(p36.3;q25) in two cases of EHE, suggesting that this may represent a recurrent abnormality in this subgroup of tumors (Mendlick et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

A novel WWTR1‐CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites

Errani

Zhang

Sung

et al. 2011

Genes Chromosomes & Cancer

456

314

View full text Add to dashboard Cite

The classification of epithelioid vascular tumors remains challenging, as there is considerable morphologic overlap between tumor subtypes, across the spectrum from benign to malignant categories. A t(1;3)(p36.3;q25) translocation was reported in two cases of epithelioid hemangioendothelioma (EHE), however, no follow-up studies have been performed to identify the gene fusion or to assess its prevalence in a larger cohort of patients. We undertook a systematic molecular analysis of 17 EHE, characterized by classic morphologic and immunophenotypic features, from various anatomic locations and with different malignant potential. For comparison we analyzed 13 epithelioid hemangiomas, five epithelioid angiosarcomas and four epithelioid sarcoma-like EHE. A fluorescence in situ hybridization (FISH) positional cloning strategy, spanning the cytogenetically defined regions on chromosomes 1p36.3 and 3q25, confirmed rearrangements in two candidate genes from these loci in all EHE cases tested. None of the other benign or malignant epithelioid vascular tumors examined demonstrated these abnormalities. Subsequent RT-PCR confirmed in three EHE the WWTR1-CAMTA1 fusion product. CAMTA1 and WWTR1 have been previously shown to play important roles in oncogenesis. Our results demonstrate the presence of a WWTR1-CAMTA1 fusion in all EHE tested from bone, soft tissue and visceral location (liver, lung) in keeping with a unique and specific pathological entity. Thus, FISH or RT-PCR analysis for the presence of WWTR1-CAMTA1 fusion may serve as a useful molecular diagnostic tool in challenging diagnoses.

show abstract

Cytogenetic analysis of a primary bone angiosarcoma

Cited by 21 publications

References 9 publications

Case report: whole exome sequencing of primary cardiac angiosarcoma highlights potential for targeted therapies

Case report: whole exome sequencing of primary cardiac angiosarcoma highlights potential for targeted therapies

Frequent FOS Gene Rearrangements in Epithelioid Hemangioma

A novel WWTR1‐CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites

Contact Info

Product

Resources

About