A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells

West, Robert B.; Rubin, Brian P.; Miller, Mary Lou; Subramanian, Subbaya; Kaygusuz, Gülşah; Montgomery, Kelli; Zhu, Shirley; Marinelli, Robert J.; Luca, Alessandro De; Downs‐Kelly, Erinn; Goldblum, John R.; Corless, Christopher L.; Brown, Patrick O.; Gilks, C. Blake; Nielsen, Torsten O.; Huntsman, David G.; Rijn, Matt van de

doi:10.1073/pnas.0507321103

Cited by 459 publications

(418 citation statements)

References 27 publications

Supporting

Mentioning

385

Contrasting

Unclassified

Order By: Relevance

“…Cytogenetic studies of TGCTs have previously revealed that 1p11-13 is frequently involved in structural aberrations (Mertens et al, 1993;Dal Cin et al, 1994;Rowlands et al, 1994;Ohjimi et al, 1996;Sciot et al, 1999;Nilsson et al, 2002) and that 2q35-37 is the most common translocation partner of chromosome 1 (Nilsson et al, 2002). These results were confirmed in a study by West et al, (2006) that additionally identified the colony-stimulating factor-1 (CSF1 or M-CSF1) locus at 1p13 as the molecular target of the chromosomal rearrangements in 20 of 23 TGCT cases. Chromosome 2 was the translocation partner in a subset (3 of 10) of the cases and collagen type VI alpha-3 (COL6A3) was identified as the gene involved at 2q37.…”

Section: Introductionsupporting

confidence: 72%

Molecular identification of COL6A3‐CSF1 fusion transcripts in tenosynovial giant cell tumors

Möller

Mandahl

Mertens

et al. 2007

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

Tenosynovial giant cell tumors (TGCTs) are benign lesions of the tendon sheaths that primarily affect the fingers, ankles, or feet. Cytogenetic data have shown that 1p13 is most frequently involved in structural aberrations and that 2q37 is its most common translocation partner. The genes involved in the translocation t(1;2)(p13;q37) were recently identified: the colonystimulating factor-1 (CSF1 or M-CSF1) at 1p13 and the collagen type VI alpha-3 (COL6A3) at 2q37. Based upon the suggestion that a fusion of these genes through the translocation would result in overexpression of CSF1 due to a strong COL6A3 promoter, we performed RT-PCR on six TGCT cases with t(1;2) to search for a putative COL6A3-CSF1 fusion gene. Such fusion transcripts were detected in three cases of which one was an in-frame fusion. In all cases, however, the breakpoints in CSF1 appeared downstream of exon 5, indicating that the amino-terminal part of CSF1, which interacts with its receptor CSF1R, is not encoded by the the chimeric transcripts we identified. The pathogenetic mechanism of these chimeric transcripts is therefore unclear. V V C 2007 Wiley-Liss, Inc.

show abstract

Section: Introductionsupporting

confidence: 72%

Molecular identification of COL6A3‐CSF1 fusion transcripts in tenosynovial giant cell tumors

Möller

Mandahl

Mertens

et al. 2007

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

show abstract

“…The 12 cases of giant cell tumor of tendon sheath/ diffuse-type giant cell tumor (GCTTS/DTGCT) were profiled as described previously. 5 Additional paraffin-embedded tumor samples from 26 cases of GCTOB, 25 cases of ABC, 15 cases of chondroblastomas, 12 cases of GCRG, 12 cases of chondromyxoid fibromas, 4 cases of hyperparathyroidism associated brown tumors, 4 cases of FD and 53 cases of GCTTS/DTGCT were collected from Stanford University Medical Center and Vancouver General Hospital. All cases of primary bone tumors were diagnosed by experienced subspecialty bone and soft-tissue pathologists at the respective centers and reviewed by a study pathologist (TON or RBW).…”

Section: Fresh-frozen Tumor and Paraffin-embedded Tumor Samplesmentioning

confidence: 99%

“…The gene expression profiles of the 12 GCTTS/DTGCT have been published previously. 5 The clinicopathologic features the six GCTOB, three ABC and four FD are shown in Table 1. All of these bone tumors represented primary lesions.…”

Section: Gene Expression Profiling Studymentioning

confidence: 99%

Gene expression profiling identifies p63 as a diagnostic marker for giant cell tumor of the bone

et al. 2008

Self Cite

View full text Add to dashboard Cite

Giant cell tumor of the bone (GCTOB) is a primary bone tumor that occurs mainly in young adults and is capable of locally aggressive growth. Its histologic appearance can resemble a number of benign and malignant tumors but no useful diagnostic marker is known currently. To identify diagnostic markers for this tumor, global gene expression profiling using cDNA microarray was performed on 6 fresh-frozen GCTOB, 3 aneurysmal bone cysts, 4 fibrous dysplasias and 12 giant cell tumors of tendon sheath/diffuse-type giant cell tumors. Unsupervised hierarchical clustering separated the tumors based on their histopathologic types, and significance analysis of microarray identified several genes including TP73L (encoding the p63 protein) that are significantly highly expressed in GCTOB relative to these other tumors. The diagnostic utility of p63 was subsequently confirmed using anti-p63 antibody on a series of 26 GCTOB, 25 aneurysmal bone cysts, 15 chondroblastomas, 13 giant cell reparative granulomas, 13 chondromyxoid fibromas, 4 brown tumors, 4 fibrous dysplasias, 53 giant cell tumors of tendon sheath/diffuse-type giant cell tumors and 385 additional mesenchymal tumors in tissue microarrays. Strong p63 nuclear staining was present in 18 of 26 (69%) GCTOB, 3 of 15 (20%) chondroblastomas and in 1 of 25 (4%) aneurysmal bone cysts while none of the other tumors commonly considered in the differential diagnosis of GCTOB showed any detectable p63 staining. Strong p63 staining is rare in bone and soft-tissue tumors in general. In contrast to the pattern of p63 staining, the majority of the chondroblastomas (70%) demonstrated S-100 immunoreactivity while only a minority of the GCTOB (8%) was immunoreactive for S-100. These findings altogether show that p63 can be used as a diagnostic marker to aid the clinical diagnosis of GCTOB.

show abstract

“…One such example is the COL1A-PDGFB fusion in dermatofibrosarcoma protuberans (DFSP) 35 and, more recently, the CSF1-COL6A3 fusion identified in giant cell tumor of tendon sheath. 36 The recurrent t(17;22)(q22;q13) resulting in COL1A-PDGFB fusion has been reported as a consistent finding in both DFSP and giant cell fibroblastoma, supporting the concept of a common pathogenetic entity. 35 The translocation fuses the strongly expressed collagen 1 alpha 1 (COL1A1) gene on chromosome 17 with the second exon of the platelet-derived growth factor-B (PDGFB) gene on chromosome 22.…”

Section: Pathologic and Molecular Features Of Imatinib Response And Imentioning

confidence: 85%

Targeted therapy of cancer: new roles for pathologists in identifying GISTs and other sarcomas

Antonescu

2008

Modern Pathology

View full text Add to dashboard Cite

Once a poorly understood pathologic entity, gastrointestinal stromal tumor (GIST) has emerged in recent years as a distinct oncologic-molecular paradigm that is now a leading model for kinase-targeted therapies in oncology. Most GISTs are KIT-expressing and KIT signaling-driven mesenchymal tumors, many of which have KIT-activating mutations. A small subset of GIST show activating mutations in PDGFRA, encoding a related member of the type III receptor tyrosine kinase family. The revelation of KIT expression as a diagnostic signature of GIST has not only revolutionized the pathologic criteria in classifying GIST, but also shed light on the histogenesis of these tumors. The similarities in KIT immunoreactivity and ultrastructural appearance between GISTs and the intestinal pacemaker, the interstitial cells of Cajal (ICC), suggested that GISTs derive from or differentiate toward the ICC lineage. KIT plays a significant role in proliferation, survival, and differentiation of hematopoietic stem cells, mast cells, melanocytes, and interstitial cells of Cajal; activating KIT mutations have been identified in tumors affecting most of these cell lineages. This review will include a summary of the biology behind the specific targeted therapies, emphasizing the central role of KIT and PDGFRA oncogenic mutations in GISTs and their clinical and pathologic correlates. The role of KIT immunohistochemistry vs mutation testing will be discussed, with an insight into the indications for KIT/PDGFRA genotyping in GIST. The morphologic and molecular changes that appear with imatinib treatment, such as response and acquired imatinib resistance, are being discussed. The success GIST story based on targeted molecular paradigm may be applied in other imatinib-responsive sarcoma, such as dermatofibrosarcoma protuberans.

show abstract

A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells

Cited by 459 publications

References 27 publications

Molecular identification of COL6A3‐CSF1 fusion transcripts in tenosynovial giant cell tumors

Molecular identification of COL6A3‐CSF1 fusion transcripts in tenosynovial giant cell tumors

Gene expression profiling identifies p63 as a diagnostic marker for giant cell tumor of the bone

Targeted therapy of cancer: new roles for pathologists in identifying GISTs and other sarcomas

Contact Info

Product

Resources

About