The t(X;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a novel gene PRCC to the TFE3 transcription factor gene

Sidhar, SK; Clark, Jeremy; Gill, S; Hamoudi, Rifat; Crew, A. Jayne; Gwilliam, Rhian; Ross, Mark T.; Linehan, W. Marston; Birdsall, Sandra; Shipley, Janet; Cooper, CS

doi:10.1093/hmg/5.9.1333

Cited by 253 publications

(169 citation statements)

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“…28 The most common translocations are t(X;1)(p11.2;q21) and t(X;17)(p11.2;q25) resulting in fusions of the TFE3 gene on Xp11.2 with PRCC in 1q21 and ASPL in 17q25, respectively. 29,30 In the studies investigating cytogenetic abnormalities in renal tumors, surgically resected material typically represented the source of tumor tissue. To our knowledge, there are no series, to date, that examined the application of cytogenetic analysis to fine-needle specimens, via karyotype analysis and/or FISH, in the diagnosis of renal neoplasms.…”

Section: Discussionmentioning

confidence: 99%

The application of cytogenetics and fluorescence in situ hybridization to fine‐needle aspiration in the diagnosis and subclassification of renal neoplasms

Roh

Cin

Silverman

et al. 2010

Cancer Cytopathology

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BACKGROUND:Percutaneous fine‐needle aspiration (FNA) cytology is an important diagnostic test for the evaluation and management of selected renal masses. Cytogenetic analysis of cytology specimens can serve as an adjunct for precise classification because certain tumors are associated with specific chromosomal aberrations. This study summarizes our experience with the application of conventional cytogenetics and fluorescence in situ hybridization (FISH) to renal FNA specimens.METHODS:All percutaneous renal FNAs performed during 2005 through 2008 were identified from the electronic pathology database. Results of cytogenetic and FISH analyses were correlated with the final diagnoses of the renal FNAs.RESULTS:A total of 303 renal FNAs were performed. During an onsite assessment, a portion of the cytology specimen was allocated for cytogenetic analysis in 74 cases. Karyotypic analysis or FISH was successful in 44 (59%) of these. Characteristic chromosomal abnormalities were observed in 27 cases. In 17 cases, a karyotype revealed a combination of trisomies/tetrasomies and in another 5 cases, FISH revealed trisomy 7 and 17, both of which are consistent with papillary renal cell carcinoma (RCC). Two cases showed 3p deletions consistent with clear cell RCC. Trisomy 3 was observed in 1 case of clear cell RCC. Monosomy 1 and 17 was observed in a case of papillary RCC comprised oncocytic cells. In 1 case of primary renal synovial sarcoma, FISH revealed a rearrangement at the SYT locus (18q11.2).CONCLUSIONS:Renal FNA specimens are amenable to analysis by cytogenetics and FISH in the diagnosis and subclassification of renal neoplasms. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

The application of cytogenetics and fluorescence in situ hybridization to fine‐needle aspiration in the diagnosis and subclassification of renal neoplasms

Roh

Cin

Silverman

et al. 2010

Cancer Cytopathology

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“…TFE3 was the first family member to be identified as a fusion oncogene (Sidhar et al 1996;Weterman et al 1996;Clark et al 1997). A significant fraction of pediatric papillary renal cell carcinomas (now termed "translocation-associated" renal cell carcinomas) was seen to harbor translocations that fused the TFE3 to a variety of alternative 5Ј partner genes.…”

Section: Mitf As An Oncogenementioning

confidence: 99%

Malignant melanoma: genetics and therapeutics in the genomic era

2006

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Cell for cell, probably no human cancer is as aggressive as melanoma. It is among a handful of cancers whose dimensions are reported in millimeters. Tumor thickness approaching 4 mm presents a high risk of metastasis, and a diagnosis of metastatic melanoma carries with it an abysmal median survival of 6-9 mo. What features of this malignancy account for such aggressive behavior? Is it the migratory history of its cell of origin or the programmed adaptation of its differentiated progeny to environmental stress, particularly ultraviolet radiation? While the answers to these questions are far from complete, major strides have been made in our understanding of the cellular, molecular, and genetic underpinnings of melanoma. More importantly, these discoveries carry profound implications for the development of therapies focused directly at the molecular engines driving melanoma, suggesting that we may have reached the brink of an unprecedented opportunity to translate basic science into clinical advances. In this review, we attempt to summarize our current understanding of the genetics and biology of this disease, drawing from expanding genomic information and lessons from development and genetically engineered mouse models. In addition, we look forward toward how these new insights will impact on therapeutic options for metastatic melanoma in the near future. The diseaseMelanomas most often arise within epidermal melanocytes of the skin, although they can also derive from noncutaneous melanocytes such as those lining the choroidal layer of the eye, GI and GU mucosal surfaces, or the meninges. Melanoma is also among the more common causes of "metastatic cancer of unknown primary," which may reflect either a propensity to arise in unexpected sites along the neural crest migratory route, or rapid growth of poorly differentiated lesions arising from indolent or unrecognized cutaneous primary lesions. Clinical staging for primary cutaneous melanoma employs measurements of thickness (in millimeters), presence of ulceration, penetration through cutaneous layers, mitotic rate, evidence of "in transit" metastasis, tumor spread to draining lymph nodes, and evidence of distant metastasis. Management issues in melanoma can be classified in terms of prevention, diagnosis, local disease management, and treatment of metastatic disease.In view of the epidemiological and emerging experimental evidence linking melanoma incidence to UV exposure and skin phototype, prevention and screening strategies represent key areas for reduction of disease incidence and severity. For most cutaneous melanomas in the so-called radial growth phase (e.g., thin melanomas), surgical removal affords curative treatment. In contrast, a significant fraction of patients diagnosed with intermediate-thickness (2-4 mm) cutaneous melanoma eventually succumb to recurrence at regional or distant sites.Critical biological questions facing the melanoma research community include: (1) What genetic and environmental factors contribute to and/or modulate risk of melanom...

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“…5,16 The TFE3/ASPSCR1 involves fusion of either exon 3 or 4 of TFE3 to ASPSCR1, which replaces the N-terminus of TFE3 but retains the DNA-binding region, activation domain, and nuclear localization signal. 17 Other known partners of TFE3 include PRCC, [18][19][20] PSF, 21 NONO, 21 or CLTC 22 resulting from t(X;1)(p11.2;q21), t(X;1)(p11.2;p34), inv(X) (p11.2q12), or t(X;17)(p11.2;q23), respectively. Each of these rearrangements provides a more robust promoter for TFE3 causing overexpression of the chimeric fusion product and a subset are known to have a stronger capacity for transactivation of other genes.…”

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confidence: 99%

Molecular cytogenetic analysis for TFE3 rearrangement in Xp11.2 renal cell carcinoma and alveolar soft part sarcoma: validation and clinical experience with 75 cases

et al. 2014

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Renal cell carcinoma with TFE3 rearrangement at Xp11.2 is a distinct subtype manifesting an indolent clinical course in children, with recent reports suggesting a more aggressive entity in adults. This subtype is morphologically heterogeneous and can be misclassified as clear cell or papillary renal cell carcinoma. TFE3 is also rearranged in alveolar soft part sarcoma. To aid in diagnosis, a break-apart strategy fluorescence in situ hybridization (FISH) probe set specific for TFE3 rearrangement and a reflex dual-color, single-fusion strategy probe set involving the most common TFE3 partner gene, ASPSCR1, were validated on formalin-fixed, paraffinembedded tissues from nine alveolar soft part sarcoma, two suspected Xp11.2 renal cell carcinoma, and nine tumors in the differential diagnosis. The impact of tissue cut artifact was reduced through inclusion of a chromosome X centromere control probe. Analysis of the UOK-109 renal carcinoma cell line confirmed the break-apart TFE3 probe set can distinguish the subtle TFE3/NONO fusion-associated inversion of chromosome X. Subsequent extensive clinical experience was gained through analysis of 75 cases with an indication of Xp11.2 renal cell carcinoma (n ¼ 54), alveolar soft part sarcoma (n ¼ 13), perivascular epithelioid cell neoplasms (n ¼ 2), chordoma (n ¼ 1), or unspecified (n ¼ 5). We observed balanced and unbalanced chromosome X;17 translocations in both Xp11.2 renal cell carcinoma and alveolar soft part sarcoma, supporting a preference but not a necessity for the translocation to be balanced in the carcinoma and unbalanced in the sarcoma. We further demonstrate the unbalanced separation is atypical, with TFE3/ASPSCR1 fusion and loss of the derivative X chromosome but also an unanticipated normal X chromosome gain in both males and females. Other diverse sex chromosome copy number combinations were observed. Our TFE3 FISH assay is a useful adjunct to morphologic analysis of such challenging cases and will be applicable to assess the growing spectrum of TFE3-rearranged tumors.

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The t(X;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a novel gene PRCC to the TFE3 transcription factor gene

Cited by 253 publications

References 27 publications

The application of cytogenetics and fluorescence in situ hybridization to fine‐needle aspiration in the diagnosis and subclassification of renal neoplasms

The application of cytogenetics and fluorescence in situ hybridization to fine‐needle aspiration in the diagnosis and subclassification of renal neoplasms

Malignant melanoma: genetics and therapeutics in the genomic era

Molecular cytogenetic analysis for TFE3 rearrangement in Xp11.2 renal cell carcinoma and alveolar soft part sarcoma: validation and clinical experience with 75 cases

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