Molecular Genetic Evidence for Different Clonal Origins of Epithelial and Stromal Components of Phyllodes Tumor of the Prostate

McCarthy, Ryan P.; Zhang, Shaobo; Bostwick, David G.; Qian, Junqi; Eble, John N.; Wang, Mingsheng; Lin, Haiqun; Liu, Cheng

doi:10.1016/s0002-9440(10)63397-4

Cited by 51 publications

(31 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[27][28][29][30][31] The criterion for allelic loss was complete or nearly complete (Z75%) absence of one allele in tumor DNA. [27][28][29][32][33][34] PCRs for each polymorphic microsatellite marker were repeated at least twice from the same DNA preparations, and the same results were obtained. Results were reported as noninformative when visual inspection could not distinguish two distinct band forms in control DNA following PCR amplification.…”

Section: Methodsmentioning

confidence: 99%

Clonal relationships between epidermotropic metastatic melanomas and their primary lesions: a loss of heterozygosity and X-chromosome inactivation-based analysis

et al. 2007

Self Cite

View full text Add to dashboard Cite

Loss of heterozygosity (LOH) has previously been demonstrated at multiple chromosome microsatellites in primary and metastatic melanomas. Epidermotropic metastases of melanoma are unique in their varied histopathologic appearance, which can mimic a primary lesion. Our objective was to compare LOH profiles in primary and epidermotropic metastatic melanoma to delineate their clonal relationship. We examined the pattern of allelic loss in the primary melanomas of nine patients in addition to the 21 corresponding epidermotropic metastatic melanomas (average 2.3 metastases per patient). DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser capture microdissection. Eight DNA microsatellite markers on six different chromosomes were analyzed: D1S214 (1p), D6S305 (6q), D9S171 (9p), D9S157 (9p), IFNA (9p), D10S212 (10q), D11S258 (11q), D18S70 (18q). In addition, X-chromosome inactivation analysis was performed in tumors from four women. LOH was seen in 67% (6/9) of primary melanomas and 81% (17/21) of epidermotropic metastatic melanomas. The most frequent allelic losses in informative cases occurred at 10q (33%), 9p (22%), and 11q (22%) in primary melanomas, and at 10q (50%), 1p (44%), and 6q (39%) in epidermotropic metastatic melanomas. Primary lesions demonstrating LOH had concordant allelic loss in at least one locus in a corresponding epidermotropic metastatic melanoma in 83% (5/6) of cases. X-chromosome analysis showed nonrandom inactivation in 75% (3/4) and 71% (5/7) of primary melanoma and epidermotropic metastatic melanoma cases, respectively. Our LOH and X-chromosome inactivation analysis data suggest that epidermotropically metastatic melanomas are clonally related to their primary lesion in many cases. Our data also indicated that some cases diagnosed as epidermotropic metastatic melanoma might be divergent clones or new primaries rather than metastatic disease.

show abstract

Section: Methodsmentioning

confidence: 99%

Clonal relationships between epidermotropic metastatic melanomas and their primary lesions: a loss of heterozygosity and X-chromosome inactivation-based analysis

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…Mutations of the p53 gene are the most common genetic abnormalities in cancer (36). PCR amplification and gel electrophoresis were done as previously described (32,33,37). The criterion for allelic loss was complete or nearly complete absence of one allele in tumor DNA (32, 33, 37 -43).…”

Section: Methodsmentioning

confidence: 99%

Molecular Evidence Supporting Field Effect in Urothelial Carcinogenesis

Jones¹,

Wang²,

Eble³

et al. 2005

Clinical Cancer Research

Self Cite

170

View full text Add to dashboard Cite

Purpose: Human urothelial carcinoma is thought to arise from a field change that affects the entire urothelium. Multifocality of urothelial carcinoma is a common finding at endoscopy and surgery. Whether these coexisting tumors arise independently or are derived from the same tumor clone is uncertain. Molecular analysis of microsatellite alterations and X-chromosome inactivation status in the cells from each coexisting tumor may further our understanding of urothelial carcinogenesis. Experimental Design: We examined 58 tumors from 21patients who underwent surgical excision for urothelial carcinoma. All patients had multiple separate foci of urothelial carcinoma (two to four) within the urinary tract. Genomic DNA samples were prepared from formalin-fixed, paraffinembedded tissue sections using laser-capture microdissection. Loss of heterozygosity (LOH) assays for three microsatellite polymorphic markers on chromosome 9p21 (IFNA and D9S171), regions of putative tumor suppressor gene p16, and on chromosome17p13 (TP53), the p53 tumor suppressor gene locus, were done. X-chromosome inactivation analysis was done on the urothelial tumors from 11female patients. Results: Seventeen of 21 (81%) cases showed allelic loss in one or more of the urothelial tumors in at least one of the three polymorphic markers analyzed. Concordant allelic loss patterns between each coexisting urothelial tumor were seen in only 3 of 21 (14%) cases. A concordant pattern of nonrandom X-chromosome inactivation in the multiple coexisting urothelial tumors was seen in only 3 of 11 female patients; of these 3 cases, only one displayed an identical allelic loss pattern in all of the tumors on LOH analysis. Conclusion: LOH and X-chromosome inactivation assays show that the coexisting tumors in many cases of multifocal urothelial carcinoma have a unique clonal origin and arise from independently transformed progenitor urothelial cells, supporting the ''field effect'' theory for urothelial carcinogenesis.

show abstract

“…Polymerase chain reaction amplification and gel electrophoresis were performed as previously described. 17,20,[27][28][29][30][31][32][33] Polymerase chain reactions for each polymorphic microsatellite marker were repeated at least twice from the same DNA preparations, and the same results were obtained.…”

Section: Detection Of Lohmentioning

confidence: 99%

Molecular Genetic Evidence for a Common Clonal Origin of Urinary Bladder Small Cell Carcinoma and Coexisting Urothelial Carcinoma

Liu

Jones

McCarthy

et al. 2005

The American Journal of Pathology

Self Cite

176

105

View full text Add to dashboard Cite

In most cases, small-cell carcinoma of the urinary bladder is admixed with other histological types of bladder carcinoma. To understand the pathogenetic relationship between the two tumor types, we analyzed histologically distinct tumor cell populations from the same patient for loss of heterozygosity (LOH) and X chromosome inactivation (in female patients). We examined five polymorphic microsatellite markers located on chromosome 3p25-26 (D3S3050), chromosome 9p21 (IFNA and D9S171), chromosome 9q32-33 (D9S177), and chromosome 17p13 (TP53) in 20 patients with small-cell carcinoma of the urinary bladder and concurrent urothelial carcinoma. DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-assisted microdissection. A nearly identical pattern of allelic loss was observed in the two tumor types in all cases, with an overall frequency of allelic loss of 90% (18 of 20 cases). Three patients showed different allelic loss patterns in the two tumor types at a single locus; however, the LOH patterns at the remaining loci were identical. Similarly, the same pattern of nonrandom X chromosome inactivation was present in both carcinoma components in the four cases analyzed. Concordant genetic alterations and X chromosome inactivation between small-cell carcinoma and coexisting urothelial carcinoma suggest that both tumor compo- Small-cell carcinoma of the urinary bladder histologically resembles that occurring in the lung and has been reported with an increasing frequency in recent years. [1][2][3][4][5][6][7][8][9][10] It has been estimated to represent 0.5% of bladder malignancies and develops more frequently in older men, with hematuria as the most common presenting symptom. 8 Small-cell carcinoma of the urinary bladder behaves aggressively, often with locally advanced or metastatic disease at the time of presentation. 11 Over the years, three principal theories have been proposed to account for the development of small-cell carcinoma in the urinary bladder. The first theory is that small-cell carcinomas originate from multipotential, undifferentiated cells or stem cells in the urothelium. 5,8,12,13 The frequent association of this tumor with coexisting urothelial carcinoma supports this theory. The second theory is that these tumors arise from neuroendocrine cells within normal or metaplastic urothelium. 14 The third theory is that small-cell carcinomas are derived from an undefined population of submucosal neuroendocrine cells. 1 In this study, we investigated the clonal relationships between small-cell carcinoma and coexisting urothelial carcinoma using loss of heterozygosity (LOH) and X chromosome inactivation analysis. Materials and Methods PatientsTwenty patients with small-cell carcinoma of the urinary bladder and concurrent urothelial carcinoma were included in our study. Archival materials from the 20 cases

show abstract

Molecular Genetic Evidence for Different Clonal Origins of Epithelial and Stromal Components of Phyllodes Tumor of the Prostate

Cited by 51 publications

References 37 publications

Clonal relationships between epidermotropic metastatic melanomas and their primary lesions: a loss of heterozygosity and X-chromosome inactivation-based analysis

Clonal relationships between epidermotropic metastatic melanomas and their primary lesions: a loss of heterozygosity and X-chromosome inactivation-based analysis

Molecular Evidence Supporting Field Effect in Urothelial Carcinogenesis

Molecular Genetic Evidence for a Common Clonal Origin of Urinary Bladder Small Cell Carcinoma and Coexisting Urothelial Carcinoma

Contact Info

Product

Resources

About