Prognostic Impact of Array-based Genomic Profiles in Esophageal Squamous Cell Cancer

Carneiro, Ana; Isinger, Anna; Karlsson, Anna; Johansson, Jan; Jönsson, Göran; Bendahl, Pär‐Ola; Falkenback, Dan; Halvarsson, Britta; Nilbert, Mef

doi:10.1186/1471-2407-8-98

Cited by 68 publications

(56 citation statements)

References 41 publications

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“…However, gain of chromosome 19 appears to be a aCGH in Metanephric Adenoma nonspecific finding, occasionally present in several different kinds of neoplasms. [28][29][30][31][32] The presence of gains of chromosome 19 in metanephric adenomas implies the existence of a yet unrecognized oncogene in this region that may have a role in the tumorigenesis of this neoplasm.…”

Section: Discussionmentioning

confidence: 99%

Detection of chromosome copy number alterations in metanephric adenomas by array comparative genomic hybridization

Pan

Epstein

2010

Modern Pathology

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Metanephric adenoma is a rare benign renal tumor typically found in adults. Previous cytogenetic analyses, including karyotyping, fluorescence in situ hybridization (FISH), and comparative genomic hybridization, have yielded conflicting results regarding the somatic genetic aberrations of these tumors. In this study, we investigated the genomic profile of nine cases of metanephric adenoma using array comparative genomic hybridization. Two cases revealed multiple chromosomal gains and losses. Three cases showed sporadic chromosomal imbalances involving no more than three chromosomes. Four cases showed normal chromosome copy numbers. The gain of chromosome 19 was the most common finding (five cases), and FISH using 19p and 19q telomeric probes further confirmed this finding. We did not observe consistent gains of chromosomes 7 and 17, which are common in papillary renal cell carcinoma, neither did we find chromosomal alterations frequently present in Wilms' tumors, including chromosome gains of 1q, 7q, and 12, and losses of 11p and 16q. Our series demonstrates that the genetic profile of metanephric adenoma is fundamentally distinct from those of papillary renal cell carcinoma and Wilms' tumor. Modern Pathology (2010) 23, 1634-1640; doi:10.1038/modpathol.2010.162; published online 27 August 2010Keywords: array comparative genomic hybridization; fluorescence in situ hybridization; metanephric adenoma On the basis of the WHO classification of renal tumors, metanephric tumors comprise metanephric adenomas, metanephric adenofibromas, and metanephric stromal tumors, 1 with each of these having its own characteristic clinicopathological presentation. Metanephric adenoma is defined as a highly cellular epithelial tumor composed of small, uniform, and embryonic-appearing cells. The tumor occurs most commonly in patients in their 50s and 60s, with a female preponderance. Although the vast majority of metanephric adenomas behave in a benign fashion, cases of regional lymph node metastasis and sarcomatoid changes have been individually reported. [2][3][4] The morphological and immunohistochemical characteristics of metanephric adenomas have been well described. 5-7 However, cytogenetic or molecular genetic data about this rare tumor are limited and have mostly been reported for single cases. Previous karyotyping of a total of five cases revealed negative findings, with the exception of a dual balanced translocation of t(1;22)(q22;13) and t(15;16)(q21;p13) in one case. 5,[8][9][10][11][12] One fluorescence in situ hybridization (FISH) study indicated gain of chromosomes 7 and 17 and loss of Y chromosome-the cytogenetic markers of papillary renal cell carcinoma-in 8 of 11 metanephric adenomas. 13 However, subsequent FISH analyses revealed normal copy numbers for chromosomes 7 and 17. 4,8,11,14,15 A deletion in chromosome 2p was the only genetic abnormality described in one tumor, and a tumor suppressor gene region on 2p13 was delineated. 16,17 Most recently, a study employing array comparative genomic hybridization (aCGH) repo...

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Section: Discussionmentioning

confidence: 99%

Detection of chromosome copy number alterations in metanephric adenomas by array comparative genomic hybridization

Pan

Epstein

2010

Modern Pathology

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“…(10,11,20,21) As expected, this focused array efficiently detected a total of 344 gains and 124 losses in most of the ESCC tumors (41 of 45 cases). Among those alterations, recurrently detected regions with CNA in ESCC ( Table 1) were part of or different from recently reported CNA regions frequently detected by aCGH in ESCC, (6,7) possibly because: (i) those reports used an oligo-array (6) or BAC-array (7) covering the entire genome, suggesting that we missed altered regions outside our probes on MCG Cancer Array-Mini; and (ii) those reports used commercially available pooled DNA from normal human men as a control for aCGH analyses, suggesting that copy-number variations frequently observed in recruited populations were detected as false-positive somatic CNA in tumors. Because (i) our focused BAC array contains regions harboring genes, whose CNA have been reported and which play important roles in carcinogenesis in various human cancers and (ii) we detected true somatic CNA by aCGH using paired tumor and non-tumorous tissues in each case, regions with CNA recurrently observed in our aCGH analysis in this study seem to be landmarks for genes biologically and clinicopathologically important to the pathogenesis of ESCC.…”

Section: Discussionmentioning

confidence: 99%

“…(2) The characterization of those alterations linked to ESCC might provide information relevant to a refined prognosis. Conventional and array-based comparative genomic hybridization (CGH and aCGH, respectively) analyses have demonstrated genetic complexity in ESCC and identified some recurrent copy-number alterations (CNA) associated with clinical parameters, particularly with survival: gain of 1p36.32, 3q11.2, 3q22.3, 5p, 5p15, 7q, 11q13.2, 12p and 19p13.3 and loss of 3p, 4p, 7q34, 9p, 9q34.3, 10q11.21, 11q and 18q21.1-q23 have been associated with a poor prognosis in univariate and/or multivariate analyses, (3)(4)(5)(6)(7) but genetic alterations and biological characteristics have so far had a limited impact on clinical prognostication and treatment. More accurate prognostic genetic markers are needed to distinguish high-risk patients from low-risk patients, so that optimal treatment can be used.…”

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confidence: 99%

Genomic copy‐number alterations of MYC and FHIT genes are associated with survival in esophageal squamous‐cell carcinoma

et al. 2012

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Esophageal squamous-cell carcinoma (ESCC) is one of the most common cancers and is associated with a poor prognosis. Studies are warranted on the clinical relevance of its genomic copy-number alterations (CNA) as prognosticators for ESCC. In the present study, we first screened recurrent CNA by array-based comparative genomic hybridization using an in-house focused bacterial artificial chromosome-based array for 108 loci in 45 ESCC specimens. We detected 14 regions showing recurrent (>20%) CNA (4 losses and 10 gains) by array-based comparative genomic hybridization in the first cohort. Among them, loss of 3p14.2 and gain of 8q24.21 for the FHIT and MYC genes, respectively, and the accumulation of those two CNA (higher FM-CNA scores) were significantly associated with a worse overall survival (OS) in the first cohort (P = 0.0273, P = 0.0356 and P = 0.0089, respectively). In the independent validation cohort of 92 resected ESCC cases, loss of FHIT, gain of MYC and higher FM-CNA scores determined by a quantitative genomic PCR-based copy-number analysis were associated with a worse OS (P = 0.0011, P = 0.0104 and P = 0.0008, respectively) and disease-free survival (P = 0.0038, P = 0.0132 and P = 0.0021, respectively). In addition, the Cox model showed the presence of either CNA to be an independent prognosticator for OS and disease-free survival in the validation cohort (P = 0.0120 and P = 0.0255, respectively). These results suggest that CNA of MYC and FHIT are poor prognostic markers, and risk stratification based on the copy-number status of those genes is useful to select the optimal treatment strategy in resected ESCC patients. (Cancer Sci 2012; 103: 1558-1566 E sophageal squamous-cell carcinoma (ESCC) is one of the most common forms of cancer and is associated with a poor prognosis.(1) Despite recent advances in diagnostic techniques and combined treatment modalities, patients with ESCC still have extremely poor survival rates, even after extended surgery. Currently, pathologic stage (pStage) is the most reliable prognostic factor for ESCC and a few molecules have been applied in a clinical setting as therapeutic and/or diagnostic biomarkers. Therefore, the significance of detecting a novel biomarker using reasonable molecules should be emphasized.Chromosomal aberration is one of several mechanisms that can lead to gene dysregulation and has long been known to play a critical role in the pathogenesis of cancers.(2) The characterization of those alterations linked to ESCC might provide information relevant to a refined prognosis. Conventional and array-based comparative genomic hybridization (CGH and aCGH, respectively) analyses have demonstrated genetic complexity in ESCC and identified some recurrent copy-number alterations (CNA) associated with clinical parameters, particularly with survival: gain of 1p36. 32, 3q11.2, 3q22.3, 5p, 5p15, 7q, 11q13.2, 12p and 19p13.3 and loss of 3p, 4p, 7q34, 9p, 9q34.3, 10q11.21, 11q and 18q21

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“…Furthermore, gene expression profile experiments revealed that the MYEOV gene was expressed in malignant PCs in 79% of newly diagnosed patients with MM, and that MYEOV is a prognostic factor, partly through a role of MYEOV in the control of neoplastic cell proliferation (11). The MYEOV gene was reported to be co-amplified and co-overexpressed with CCND1 in a subset of esophageal squamous cell carcinomas, breast cancers, gastric cancers, neuroblastomas and colorectal cancers (12,13). The oncogenic role of MYEOV has also been investigated in functional studies, where in vitro small interfering RNA-mediated knockdown of MYEOV resulted in an inhibition of the proliferation, invasion and migration of colorectal cancer cell lines (13).…”

Section: Discussionmentioning

confidence: 99%

MYEOV gene overexpression in primary plasma cell leukemia with t(11;14)(q13;q32)

et al. 2016

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Abstract. Primary plasma cell leukemia (pPCL) is an uncommon form of plasma cell dyscrasia, and the most aggressive of the human monoclonal gammopathies. The t(11;14)(q13;q32) rearrangement is the most common alteration in pPCL, promoting cyclin D1 (CCND1) gene overexpression caused by its juxtaposition with the immunoglobulin heavy locus chromosome region. The myeloma overexpressed (MYEOV) gene maps very close to the CCND1 gene on chromosome 11, but its overexpression is rarely observed in multiple myeloma. The present study describes a case of pPCL with t(11;14) characterized by a breakpoint on der(11), unlike the one usually observed. Droplet digital polymerase chain reaction analysis revealed overexpression of CCND1 and MYEOV. To the best of our knowledge, MYEOV gene overexpression has never been previously described in pPCL. IntroductionPrimary plasma cell leukemia (pPCL) is an uncommon form of plasma cell (PC) dyscrasia, and the most aggressive of the human monoclonal gammopathies (1,2). pPCL is characterized by the presence of >20% circulating PCs in peripheral blood and/or an absolute circulating PC count exceeding 2x10 9 cells/l (1). Peripheral blood flow cytometry is an important tool to demonstrate the presence of PCs and to confirm their clonality, as well as to exclude other lymphoproliferative disorders such as low-grade B-cell and lymphoplasmacytic lymphoma (2). In regard to cytogenetic findings, the t(11;14)(q13;q32) rearrangement is the most common alteration in pPCL (3), promoting cyclin D1 (CCND1) gene overexpression due to its juxtaposition with the immunoglobulin heavy locus (IGH) chromosome region. The subsequent deregulation of CCND1 is considered to perturb the G1-S phase transition of the cell cycle and, therefore, to contribute to tumor development (4). However, the IGH/CCND1 rearrangement alone may be insufficient to cause hematologic malignancies, and may require other additional genetic aberrations to boost its oncogenic activity (4). In the present study, a case of pPCL with t(11;14) characterized by the overexpression of CCND1 and the myeloma overexpressed (MYEOV) gene, which maps very close CCND1 on chromosome 11, is described. Materials and methodsClinical history. In July 2014, a previously healthy 65-year-old male was admitted to the Department of Emergency and Organ Transplantation, Hematology Section, University of Bari (Bari, Italy) for anemia, thrombocytopenia and mild leukocytosis [hemoglobin levels, 11.0 g/dl (normal range, 13.0-16.0 g/dl); platelets, 49x10 9 cells/l (normal range, 150-450x10 9 cells/l); and leukocytes, 13x10 9 cells/l (normal range, 4-10x10 9 cells/l)]. Peripheral blood smear analysis demonstrated the presence of ~40% apparently undifferentiated cells, a number of which had a large eccentric nucleus and scattered chromatin, while others had a scanty and intensely basophilic cytoplasm with protrusions (Fig. 1A-C). Immunophenotypic analysis of bone marrow (BM) demonstrated the specimen to be cluster of differentiation (CD)38+, CD138+, CD20-, CD23-, CD56+, ...

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Prognostic Impact of Array-based Genomic Profiles in Esophageal Squamous Cell Cancer

Cited by 68 publications

References 41 publications

Detection of chromosome copy number alterations in metanephric adenomas by array comparative genomic hybridization

Detection of chromosome copy number alterations in metanephric adenomas by array comparative genomic hybridization

Genomic copy‐number alterations of MYC and FHIT genes are associated with survival in esophageal squamous‐cell carcinoma

MYEOV gene overexpression in primary plasma cell leukemia with t(11;14)(q13;q32)

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