Association between Large-scale Genomic Homozygosity without Chromosomal Loss and Nonseminomatous Germ Cell Tumor Development

Lu, Yong‐Jie; Yang, Junyao; Noël, Elodie; Skoulakis, Spyros; Chaplin, Tracy; Raghavan, Manoj; Purkis, T.; McIntyre, Alan; Kudahetti, Sakunthala C.; Naase, Mahmoud; Berney, Daniel M.; Shipley, Janet; Oliver, R. T. D.; Young, Bryan D.

doi:10.1158/0008-5472.can-05-1697

Cited by 11 publications

(7 citation statements)

References 18 publications

(19 reference statements)

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“…The combination of both allelotyping and copy number analysis for each locus allowed us to identify one tumor with LOH of two chromosomes without copy number loss, suggesting uniparental disomy of chromosomes either due to nondisjunction event followed by chromosomal duplication or a recombination. These alterations have been reported in acute lymphoblastic leukemias (Irving et al, 2005;Raghavan et al, 2005) and PETs , and are common in nonseminomatous germ cell tumors (Lu et al, 2005). These alterations cannot be detected by methodology that utilizes chromosomal copy number alone, such as comparative genomic hybridization or in situ hybridization.…”

Section: Discussionmentioning

confidence: 95%

Allelic alterations in well‐differentiated neuroendocrine tumors (carcinoid tumors) identified by genome‐wide single nucleotide polymorphism analysis and comparison with pancreatic endocrine tumors

Kim

Nagano

Choi

et al. 2007

Genes Chromosomes & Cancer

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Well-differentiated neuroendocrine tumors (WDNT, carcinoid tumors) are uncommon indolent neoplasms. The genetic alterations of these tumors are not well characterized. We used genome-wide high-density single nucleotide polymorphism (SNP) array analysis to detect copy number alterations in 29 WDNTs, including seven lung, seven nonileal gastrointestinal, and 15 ileal tumors, and compared with allelic imbalances in 15 pancreatic endocrine tumors (PETs). Most frequent allelic imbalances in WDNTs were losses of chromosome 18 in 10 tumors (34%), chromosome 21 or 21q in six (21%), chromosome 13 or 13q in five (17%) and chromosome 16 or 16q in four (14%) tumors, and amplification of chromosome 20 or 20p in seven (24%) tumors. We also found one tumor with loss of heterozygosity of chromosomes 10 and 15 without copy number loss. These allelic imbalances were associated with primary site of tumor: loss of chromosome 18 was present exclusively in ileal WDNTs (P 5 0.001), and loss of chromosome 21 or 21q was more frequent in nonileal gastrointestinal WDNTs (P 5 0.02). The tumors with loss of chromosome 21 were larger compared to tumors without loss (P 5 0.03). Chromosomal aberrations were less common in WDNTs from lung and gastrointestinal tract compared to PETs (P 5 0.001). Our study shows that genome-wide allelotyping using SNP array is a powerful new tool for the analysis of allelic imbalances in WDNTs, and some of these alterations are tumor site-dependent and are different than in PETs. V V C 2007 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 95%

Allelic alterations in well‐differentiated neuroendocrine tumors (carcinoid tumors) identified by genome‐wide single nucleotide polymorphism analysis and comparison with pancreatic endocrine tumors

Kim

Nagano

Choi

et al. 2007

Genes Chromosomes & Cancer

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“…Also the combination of both allelotyping and copy number analysis for each locus allowed us to identify uniparental disomy of chromosomes in two tumors due to either a non-disjunction event followed by chromosomal duplication or to a recombination. These alterations have been reported in acute lymphoblastic leukemias (Irving et al 2005), and are common in non-seminomatous germ cell tumors (Lu et al 2005) and basal cell carcinomas (Teh et al 2005). These alterations cannot be detected by methodology that utilizes chromosomal copy number alone, such as comparative genomic hybridization or in situ hybridization.…”

Section: Discussionmentioning

confidence: 99%

“…Allelic imbalances (AI) may be detected by a variety of methods including karyotyping, comparative genomic hybridization, and microsatellite analysis, but these are either of low resolution or laborious to conduct on a genome-wide scale. In contrast, single nucleotide polymorphism (SNP) allelotyping is a sensitive method to detect DNA copy number and chromosomal loss of heterozygosity (LOH; Matsuzaki et al 2004, Zhao et al 2004, Irving et al 2005, Lu et al 2005, Nannya et al 2005, Teh et al 2005. This method has been used to determine AI in a variety of tumors (Lu et al 2005, Teh et al 2005, leukemias (Irving et al 2005), and in a variety of tumor cell lines (Matsuzaki et al 2004, Zhao et al 2004, Nannya et al 2005.…”

Section: Introductionmentioning

confidence: 99%

Allelic alterations in pancreatic endocrine tumors identified by genome-wide single nucleotide polymorphism analysis

Nagano¹,

Kim²,

Zhang³

et al. 2007

Endocr Relat Cancer

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Pancreatic endocrine tumors (PETs) are uncommon and the genetic alterations in these indolent tumors are not well characterized. Chromosomal imbalances are frequent in tumors but PETs have not been studied by high-density single nucleotide polymorphism (SNP) array. We used genome-wide high-density SNP array analysis to detect copy number alterations using matched tumor and non-neoplastic tissue samples from 15 patients with PETs. In our study, whole or partial loss of chromosomes 1, 3, 11, 22 was present in 40, 47, 53, 40% of tumors respectively, and gain of chromosomes 5, 7, 12, 14, 17, and 20 was present in 47, 60, 47, 53, 53, and 47% of tumors respectively. One tumor had loss of heterozygosity of chromosome 3 and another of chromosome 22 without copy number alterations, suggesting uniparental disomy due to non-disjunction and deletion or to chromosomal recombination. Chromosomal aberrations of the autosomal chromosomes were correlated with chromosomal loss or gain of other chromosomes (rO0.5, P!0.5). About 60% of PETs had high allelic imbalances (AI) defined by more than four chromosomal aberrations, and 40% of tumors had low AI. The PETs with high AI were larger: the mean tumor size with high AI was 5.4G3.1 cm compared with 2.3G1.3 cm for low AI (PZ0.03). Our study shows that genome-wide allelotyping is a powerful new tool for the analysis of AI in PETs.

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“…All of the parental cell lines were made resistant to cisplatin by long-term exposure to the drug. The TGCT cell lines have previously been analyzed by single nucleotide polymorphism arrays 22,23 and karyotyped by 24-color fluorescence in situ hybridization (unpublished data). The genomic alterations were similar to those detected in the original cell lines using low resolution genetic analyses soon after they were established, including the gain of 12p which is specific for TGCTs.…”

Section: Cell Lines and Clinical Samplesmentioning

confidence: 99%

The Association of CCND1 Overexpression and Cisplatin Resistance in Testicular Germ Cell Tumors and Other Cancers

Noël

Yeste‐Velasco

Mao

et al. 2010

The American Journal of Pathology

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Development of chemoresistance limits the clinical efficiency of platinum-based therapy. Although many resistance mechanisms have been demonstrated, genetic/molecular alterations responsible for drug resistance in the majority of clinical cases have not been identified. We analyzed three pairs of testicular germ cell tumor cell lines using Affymetrix expression microarrays and revealed a limited number of differentially expressed genes across the cell lines when comparing the parental and resistant cells. Among them, CCND1 was the most significantly differentially expressed gene. Analysis of testicular germ cell tumor clinical samples by quantitative reverse transcription PCR analysis revealed that overall expression of CCND1 was significantly higher in resistant cases compared with sensitive samples (P < 0.0001). We also found that CCND1 was dramatically overexpressed both in induced and intrinsically resistant samples of ovarian and prostate cancer. Finally combined CCND1 knockdown using small-interfering RNA and cisplatin treatment inhibited cell growth in vitro significantly more effectively than any of these single treatments. Therefore, deregulation of CCND1 may be a major cause of cisplatin resistance in testicular germ cell tumors and may also be implicated in ovarian and prostate cancers. CCND1 could be potentially used as a marker for treatment stratification and as a molecular target to improve the treatment of platinum-resistant tumors. Cisplatin has dramatically improved the clinical outcome for testicular germ cell tumors (TGCTs) and remains the first line treatment of several other solid tumors such as, ovarian, breast, head and neck, and small cell lung cancers.

show abstract

Association between Large-scale Genomic Homozygosity without Chromosomal Loss and Nonseminomatous Germ Cell Tumor Development

Cited by 11 publications

References 18 publications

Allelic alterations in well‐differentiated neuroendocrine tumors (carcinoid tumors) identified by genome‐wide single nucleotide polymorphism analysis and comparison with pancreatic endocrine tumors

Allelic alterations in well‐differentiated neuroendocrine tumors (carcinoid tumors) identified by genome‐wide single nucleotide polymorphism analysis and comparison with pancreatic endocrine tumors

Allelic alterations in pancreatic endocrine tumors identified by genome-wide single nucleotide polymorphism analysis

The Association of CCND1 Overexpression and Cisplatin Resistance in Testicular Germ Cell Tumors and Other Cancers

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