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31 results on '"Pflueger, Dorothee"'

1. Data from Characterization of KRAS Rearrangements in Metastatic Prostate Cancer

Author

Wang, Xiao-Song, primary, Shankar, Sunita, primary, Dhanasekaran, Saravana M., primary, Ateeq, Bushra, primary, Sasaki, Atsuo T., primary, Jing, Xiaojun, primary, Robinson, Daniel, primary, Cao, Qi, primary, Prensner, John R., primary, Yocum, Anastasia K., primary, Wang, Rui, primary, Fries, Daniel F., primary, Han, Bo, primary, Asangani, Irfan A., primary, Cao, Xuhong, primary, Li, Yong, primary, Omenn, Gilbert S., primary, Pflueger, Dorothee, primary, Gopalan, Anuradha, primary, Reuter, Victor E., primary, Kahoud, Emily Rose, primary, Cantley, Lewis C., primary, Rubin, Mark A., primary, Palanisamy, Nallasivam, primary, Varambally, Sooryanarayana, primary, and Chinnaiyan, Arul M., primary

Published
2023
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2. Supplementary Methods and Data (posted 7/5/2011) from Characterization of KRAS Rearrangements in Metastatic Prostate Cancer

Author

Wang, Xiao-Song, primary, Shankar, Sunita, primary, Dhanasekaran, Saravana M., primary, Ateeq, Bushra, primary, Sasaki, Atsuo T., primary, Jing, Xiaojun, primary, Robinson, Daniel, primary, Cao, Qi, primary, Prensner, John R., primary, Yocum, Anastasia K., primary, Wang, Rui, primary, Fries, Daniel F., primary, Han, Bo, primary, Asangani, Irfan A., primary, Cao, Xuhong, primary, Li, Yong, primary, Omenn, Gilbert S., primary, Pflueger, Dorothee, primary, Gopalan, Anuradha, primary, Reuter, Victor E., primary, Kahoud, Emily Rose, primary, Cantley, Lewis C., primary, Rubin, Mark A., primary, Palanisamy, Nallasivam, primary, Varambally, Sooryanarayana, primary, and Chinnaiyan, Arul M., primary

Published
2023
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3. Supplementary Methods, Figures, Tables, and References from Characterization of KRAS Rearrangements in Metastatic Prostate Cancer

Author

Wang, Xiao-Song, primary, Shankar, Sunita, primary, Dhanasekaran, Saravana M., primary, Ateeq, Bushra, primary, Sasaki, Atsuo T., primary, Jing, Xiaojun, primary, Robinson, Daniel, primary, Cao, Qi, primary, Prensner, John R., primary, Yocum, Anastasia K., primary, Wang, Rui, primary, Fries, Daniel F., primary, Han, Bo, primary, Asangani, Irfan A., primary, Cao, Xuhong, primary, Li, Yong, primary, Omenn, Gilbert S., primary, Pflueger, Dorothee, primary, Gopalan, Anuradha, primary, Reuter, Victor E., primary, Kahoud, Emily Rose, primary, Cantley, Lewis C., primary, Rubin, Mark A., primary, Palanisamy, Nallasivam, primary, Varambally, Sooryanarayana, primary, and Chinnaiyan, Arul M., primary

Published
2023
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4. Supplementary Figure 2 from SLC45A3-ELK4 Is a Novel and Frequent Erythroblast Transformation–Specific Fusion Transcript in Prostate Cancer

Author

Rickman, David S., primary, Pflueger, Dorothee, primary, Moss, Benjamin, primary, VanDoren, Vanessa E., primary, Chen, Chen X., primary, de la Taille, Alexandre, primary, Kuefer, Rainer, primary, Tewari, Ashutosh K., primary, Setlur, Sunita R., primary, Demichelis, Francesca, primary, and Rubin, Mark A., primary

Published
2023
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5. Supplementary Figure 1 from SLC45A3-ELK4 Is a Novel and Frequent Erythroblast Transformation–Specific Fusion Transcript in Prostate Cancer

Author

Rickman, David S., primary, Pflueger, Dorothee, primary, Moss, Benjamin, primary, VanDoren, Vanessa E., primary, Chen, Chen X., primary, de la Taille, Alexandre, primary, Kuefer, Rainer, primary, Tewari, Ashutosh K., primary, Setlur, Sunita R., primary, Demichelis, Francesca, primary, and Rubin, Mark A., primary

Published
2023
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6. Supplementary Figure Legends 1-2, Methods from SLC45A3-ELK4 Is a Novel and Frequent Erythroblast Transformation–Specific Fusion Transcript in Prostate Cancer

Author

Rickman, David S., primary, Pflueger, Dorothee, primary, Moss, Benjamin, primary, VanDoren, Vanessa E., primary, Chen, Chen X., primary, de la Taille, Alexandre, primary, Kuefer, Rainer, primary, Tewari, Ashutosh K., primary, Setlur, Sunita R., primary, Demichelis, Francesca, primary, and Rubin, Mark A., primary

Published
2023
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9. Testing mutual exclusivity of ETS rearranged prostate cancer

Author

Svensson, Maria A, LaFargue, Christopher J, MacDonald, Theresa Y, Pflueger, Dorothee, Kitabayashi, Naoki, Santa-Cruz, Ashley M, Garsha, Karl E, Sathyanarayana, Ubaradka G, Riley, Janice P, Yun, Chol S, Nagy, Dea, Kosmeder, Jerry W, Pestano, Gary A, Tewari, Ashutosh K, Demichelis, Francesca, and Rubin, Mark A

Published
2011
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10. The genomic complexity of primary human prostate cancer

Author

Berger, Michael F., Lawrence, Michael S., Demichelis, Francesca, Drier, Yotam, Cibulskis, Kristian, Sivachenko, Andrey Y., Sboner, Andrea, Esgueva, Raquel, Pflueger, Dorothee, Sougnez, Carrie, Onofrio, Robert, Carter, Scott L., Park, Kyung, Habegger, Lukas, Ambrogio, Lauren, Fennell, Timothy, Parkin, Melissa, Saksena, Gordon, Voet, Douglas, Ramos, Alex H., Pugh, Trevor J., Wilkinson, Jane, Fisher, Sheila, Winckler, Wendy, Mahan, Scott, Ardlie, Kristin, Baldwin, Jennifer, Simons, Jonathan W., Kitabayashi, Naoki, MacDonald, Theresa Y., Kantoff, Philip W., Chin, Lynda, Gabriel, Stacey B., Gerstein, Mark B., Golub, Todd R., Meyerson, Matthew, Tewari, Ashutosh, Lander, Eric S., Getz, Gad, Rubin, Mark A., and Garraway, Levi A.

Published
2011
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14. Functional characterization of BC039389-GATM and KLK4-KRSP1 chimeric read-through transcripts which are up-regulated in renal cell cancer

Author

Pflueger, Dorothee, Mittmann, Christiane, Dehler, Silvia, Rubin, Mark A, Moch, Holger, Schraml, Peter, Pflueger, Dorothee, Mittmann, Christiane, Dehler, Silvia, Rubin, Mark A, Moch, Holger, and Schraml, Peter

Abstract

BACKGROUND: Chimeric read-through RNAs are transcripts originating from two directly adjacent genes (<10 kb) on the same DNA strand. Although they are found in next-generation whole transcriptome sequencing (RNA-Seq) data on a regular basis, investigating them further has usually been refrained from. Therefore, their expression patterns or functions in general, and in oncogenesis in particular, are poorly understood. RESULTS: We used paired-end RNA-Seq and a specifically designed computational data analysis pipeline (FusionSeq) to nominate read-through events in a small discovery set of renal cell carcinomas (RCC) and confirmed them in a larger validation cohort. 324 read-through events were called overall; 22/27 (81%) selected nominees passed validation with conventional PCR and were sequenced at the junction region. We frequently identified various isoforms of a given read-through event. 2/22 read-throughs were up-regulated: BC039389-GATM was higher expressed in RCC compared to benign adjacent kidney; KLK4-KRSP1 was expressed in 46/169 (27%) RCCs, but rarely in normal tissue. KLK4-KRSP1 expression was associated with worse clinical outcome in the patient cohort. In cell lines, both read-throughs influenced molecular mechanisms (i.e. target gene expression or migration/invasion) in a way that counteracted the effect of the respective parent transcript GATM or KLK4. CONCLUSIONS: Our data suggests that the up-regulation of read-through RNA chimeras in tumors is not random but causes regulatory effects on cellular mechanisms and may impact patient survival.

Published
2015

16. N-myc Downstream Regulated Gene 1 (NDRG1) Is Fused to ERG in Prostate Cancer12

Author

Pflueger, Dorothee, Rickman, David S, Sboner, Andrea, Perner, Sven, LaFargue, Christopher J, Svensson, Maria A, Moss, Benjamin J, Kitabayashi, Naoki, Pan, Yihang, de la Taille, Alexandre, Kuefer, Rainer, Tewari, Ashutosh K, Demichelis, Francesca, Chee, Mark S, Gerstein, Mark B, and Rubin, Mark A

Subjects
Male, genetic structures, Base Sequence, Estradiol, Oncogene Proteins, Fusion, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Molecular Sequence Data, Intracellular Signaling Peptides and Proteins, Gene Expression, Prostatic Neoplasms, Androgen Antagonists, Cell Cycle Proteins, Estrogens, urologic and male genital diseases, eye diseases, Flutamide, Gene Expression Regulation, Neoplastic, Transcriptional Regulator ERG, Biomarkers, Tumor, Trans-Activators, Humans, sense organs, In Situ Hybridization, Fluorescence, Research Article
Abstract

A step toward the molecular classification of prostate cancer was the discovery of recurrent erythroblast transformation-specific rearrangements, most commonly fusing the androgen-regulated TMPRSS2 promoter to ERG. The TMPRSS2-ERG fusion is observed in around 90% of tumors that overexpress the oncogene ERG. The goal of the current study was to complete the characterization of these ERG-overexpressing prostate cancers. Using fluorescence in situ hybridization and reverse transcription-polymerase chain reaction assays, we screened 101 prostate cancers, identifying 34 cases (34%) with the TMPRSS2-ERG fusion. Seven cases demonstrated ERG rearrangement by fluorescence in situ hybridization without the presence of TMPRSS2-ERG fusion messenger RNA transcripts. Screening for known 5' partners, we determined that three cases harbored the SLC45A3-ERG fusion. To discover novel 5' partners in these ERG-overexpressing and ERG-rearranged cases, we used paired-end RNA sequencing. We first confirmed the utility of this approach by identifying the TMPRSS2-ERG fusion in a known positive prostate cancer case and then discovered a novel fusion involving the androgen-inducible tumor suppressor, NDRG1 (N-myc downstream regulated gene 1), and ERG in two cases. Unlike TMPRSS2-ERG and SCL45A3-ERG fusions, the NDRG1-ERG fusion is predicted to encode a chimeric protein. Like TMPRSS2, SCL45A3 and NDRG1 are inducible not only by androgen but also by estrogen. This study demonstrates that most ERG-overexpressing prostate cancers harbor hormonally regulated TMPRSS2-ERG, SLC45A3-ERG, or NDRG1-ERG fusions. Broader implications of this study support the use of RNA sequencing to discover novel cancer translocations.

Published
2009

17. SLC45A3-ELK4 is a Novel and Frequent ETS Fusion Transcript in Prostate Cancer

Author

Rickman, David S., Pflueger, Dorothee, Moss, Benjamin, VanDoren, Vanessa E., Chen, Chen X., de la Taille, Alexandre, Kuefer, Rainer, Tewari, Ashutosh K., Setlur, Sunita R., Demichelis, Francesca, and Rubin, Mark A.

Subjects
Male, Oncogene Proteins, Fusion, Proto-Oncogene Proteins c-ets, Transcription, Genetic, Prostatic Neoplasms, Metribolone, Article, Gene Expression Regulation, Neoplastic, Chromosomes, Human, Pair 1, Cell Line, Tumor, Humans, RNA, Messenger, Chromosome Deletion, Testosterone Congeners, In Situ Hybridization, Fluorescence
Abstract

Chromosomal rearrangements account for all erythroblast transformation-specific (ETS) family member gene fusions that have been reported in prostate cancer and have clinical, diagnostic, and prognostic implications. Androgen-regulated genes account for the majority of the 5' genomic regulatory promoter elements fused with ETS genes. TMPRSS2-ERG, TMPRSS2-ETV1, and SLC45A3-ERG rearrangements account for roughly 90% of ETS fusion prostate cancer. ELK4, another ETS family member, is androgen regulated, involved in promoting cell growth, and highly expressed in a subset of prostate cancer, yet the mechanism of ELK4 overexpression is unknown. In this study, we identified a novel ETS family fusion transcript, SLC45A3-ELK4, and found it to be expressed in both benign prostate tissue and prostate cancer. We found high levels of SLC45A3-ELK4 mRNA restricted to a subset of prostate cancer samples. SLC45A3-ELK4 transcript can be detected at high levels in urine samples from men at risk for prostate cancer. Characterization of the fusion mRNA revealed a major variant in which SLC45A3 exon 1 is fused to ELK4 exon 2. Based on quantitative PCR analyses of DNA, unlike other ETS fusions described in prostate cancer, the expression of SLC45A3-ELK4 mRNA is not exclusive to cases harboring a chromosomal rearrangement. Treatment of LNCaP cancer cells with a synthetic androgen (R1881) revealed that SLC45A3-ELK4, and not endogenous ELK4, mRNA expression is androgen regulated. Altogether, our findings show that SLC45A3-ELK4 mRNA expression is heterogeneous, highly induced in a subset of prostate cancers, androgen regulated, and most commonly occurs through a mechanism other than chromosomal rearrangement (e.g., trans-splicing).

Published
2009

18. Testing mutual exclusivity of ETS rearranged prostate cancer

Author

Svensson, Maria A., LaFargue, Christopher J., MacDonald, Theresa Y., Pflueger, Dorothee, Kitabayashi, Naoki, Santa-Cruz, Ashley M., Garsha, Karl E., Sathyanarayana, Ubaradka G., Riley, Janice P., Yun, Chol S., Nagy, Dea, Kosmeder, Jerry W., Pestano, Gary A., Tewari, Ashutosh K., Demichelis, Francesca, Rubin, Mark A., Svensson, Maria A., LaFargue, Christopher J., MacDonald, Theresa Y., Pflueger, Dorothee, Kitabayashi, Naoki, Santa-Cruz, Ashley M., Garsha, Karl E., Sathyanarayana, Ubaradka G., Riley, Janice P., Yun, Chol S., Nagy, Dea, Kosmeder, Jerry W., Pestano, Gary A., Tewari, Ashutosh K., Demichelis, Francesca, and Rubin, Mark A.

Abstract

Prostate cancer is a clinically heterogeneous and multifocal disease. More than 80% of patients with prostate cancer harbor multiple geographically discrete cancer foci at the time of diagnosis. Emerging data suggest that these foci are molecularly distinct consistent with the hypothesis that they arise as independent clones. One of the strongest arguments is the heterogeneity observed in the status of E26 transformation specific (ETS) rearrangements between discrete tumor foci. The clonal evolution of individual prostate cancer foci based on recent studies demonstrates intertumoral heterogeneity with intratumoral homogeneity. The issue of multifocality and interfocal heterogeneity is important and has not been fully elucidated due to lack of the systematic evaluation of ETS rearrangements in multiple tumor sites. The current study investigates the frequency of multiple gene rearrangements within the same focus and between different cancer foci. Fluorescence in situ hybridization (FISH) assays were designed to detect the four most common recurrent ETS gene rearrangements. In a cohort of 88 men with localized prostate cancer, we found ERG, ETV1, and ETV5 rearrangements in 51% (44/86), 6% (5/85), and 1% (1/86), respectively. None of the cases demonstrated ETV4 rearrangements. Mutual exclusiveness of ETS rearrangements was observed in the majority of cases; however, in six cases, we discovered multiple ETS or 50 fusion partner rearrangements within the same tumor focus. In conclusion, we provide further evidence for prostate cancer tumor heterogeneity with the identification of multiple concurrent gene rearrangements. Laboratory Investigation (2011) 91, 404-412; doi: 10.1038/labinvest.2010.179; published online 25 October 2010

Published
2011
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19. Characterization of KRAS Rearrangements in Metastatic Prostate Cancer

Author

Wang, Xiao-Song, primary, Shankar, Sunita, additional, Dhanasekaran, Saravana M., additional, Ateeq, Bushra, additional, Sasaki, Atsuo T., additional, Jing, Xiaojun, additional, Robinson, Daniel, additional, Cao, Qi, additional, Prensner, John R., additional, Yocum, Anastasia K., additional, Wang, Rui, additional, Fries, Daniel F., additional, Han, Bo, additional, Asangani, Irfan A., additional, Cao, Xuhong, additional, Li, Yong, additional, Omenn, Gilbert S., additional, Pflueger, Dorothee, additional, Gopalan, Anuradha, additional, Reuter, Victor E., additional, Kahoud, Emily Rose, additional, Cantley, Lewis C., additional, Rubin, Mark A., additional, Palanisamy, Nallasivam, additional, Varambally, Sooryanarayana, additional, and Chinnaiyan, Arul M., additional

Published
2011
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20. Abstract 3925: Characterization of complex chromosomal aberrations in prostate cancer from whole genome sequencing

Author

Berger, Michael F., primary, Lawrence, Michael S., additional, Demichelis, Francesca, additional, Drier, Yotam, additional, Cibulskis, Kristian, additional, Sivachenko, Andrey Y., additional, Sboner, Andrea, additional, Esgueva, Raquel, additional, Pflueger, Dorothee, additional, Sougnez, Carrie, additional, Onofrio, Robert, additional, Carter, Scott L., additional, Park, Kyung, additional, Habegger, Lukas, additional, Ambrogio, Lauren, additional, Fennell, Timothy, additional, Parkin, Melissa, additional, Saksena, Gordon, additional, Voet, Douglas, additional, Ramos, Alex H., additional, Pugh, Trevor J., additional, Wilkinson, Jane, additional, Fisher, Sheila, additional, Winckler, Wendy, additional, Mahan, Scott, additional, Ardlie, Kristin, additional, Baldwin, Jennifer, additional, Simons, Jonathan W., additional, Kitabayashi, Naoki, additional, MacDonald, Theresa Y., additional, Kantoff, Philip W., additional, Chin, Lynda, additional, Gabriel, Stacey B., additional, Gerstein, Mark B., additional, Golub, Todd R., additional, Meyerson, Matthew, additional, Tewari, Ashutosh, additional, Lander, Eric S., additional, Getz, Gad, additional, Rubin, Mark A., additional, and Garraway, Levi A., additional

Published
2011
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21. Discovery of non-ETS gene fusions in human prostate cancer using next-generation RNA sequencing

Author

Pflueger, Dorothee, primary, Terry, Stéphane, additional, Sboner, Andrea, additional, Habegger, Lukas, additional, Esgueva, Raquel, additional, Lin, Pei-Chun, additional, Svensson, Maria A., additional, Kitabayashi, Naoki, additional, Moss, Benjamin J., additional, MacDonald, Theresa Y., additional, Cao, Xuhong, additional, Barrette, Terrence, additional, Tewari, Ashutosh K., additional, Chee, Mark S., additional, Chinnaiyan, Arul M., additional, Rickman, David S., additional, Demichelis, Francesca, additional, Gerstein, Mark B., additional, and Rubin, Mark A., additional

Published
2010
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22. Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma

Author

Palanisamy, Nallasivam, primary, Ateeq, Bushra, additional, Kalyana-Sundaram, Shanker, additional, Pflueger, Dorothee, additional, Ramnarayanan, Kalpana, additional, Shankar, Sunita, additional, Han, Bo, additional, Cao, Qi, additional, Cao, Xuhong, additional, Suleman, Khalid, additional, Kumar-Sinha, Chandan, additional, Dhanasekaran, Saravana M, additional, Chen, Ying-bei, additional, Esgueva, Raquel, additional, Banerjee, Samprit, additional, LaFargue, Christopher J, additional, Siddiqui, Javed, additional, Demichelis, Francesca, additional, Moeller, Peter, additional, Bismar, Tarek A, additional, Kuefer, Rainer, additional, Fullen, Douglas R, additional, Johnson, Timothy M, additional, Greenson, Joel K, additional, Giordano, Thomas J, additional, Tan, Patrick, additional, Tomlins, Scott A, additional, Varambally, Sooryanarayana, additional, Rubin, Mark A, additional, Maher, Christopher A, additional, and Chinnaiyan, Arul M, additional

Published
2010
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23. Abstract 1139: Complete characterization of prostate cancer genomes by massively parallel sequencing

Author

Berger, Michael F., primary, Lawrence, Michael S., additional, Cibulskis, Kristian, additional, Pflueger, Dorothee, additional, Demichelis, Francesca, additional, Sougnez, Carrie, additional, Onofrio, Robert C., additional, Ambrogio, Lauren, additional, Fennell, Timothy, additional, Parkin, Melissa, additional, Carter, Scott L., additional, Saksena, Gordon, additional, Sivachenko, Andrey, additional, Voet, Douglas, additional, Wilkinson, Jane, additional, Fisher, Sheila, additional, Winckler, Wendy, additional, Ardlie, Kristin, additional, Chant, John, additional, Baldwin, Jennifer, additional, Gerstein, Mark, additional, Golub, Todd R., additional, Meyerson, Matthew, additional, Tewari, Ashutosh K., additional, Gabriel, Stacey B., additional, Lander, Eric S., additional, Getz, Gad, additional, Rubin, Mark A., additional, and Garraway, Levi A., additional

Published
2010
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24. Abstract 2743: Accelerating the exploration of novel gene fusion events in prostate cancer

Author

Pflueger, Dorothee, primary, Terry, Stephane, additional, Sboner, Andrea, additional, Habegger, Lukas, additional, Esgueva, Raquel, additional, Svensson, Maria A., additional, Lin, Pei-Chun, additional, Kitabayashi, Naoki, additional, Moss, Benjamin J., additional, Tewari, Ashutosh K., additional, Chee, Mark S., additional, Demichelis, Francesca, additional, Gerstein, Mark B., additional, and Rubin, Mark A., additional

Published
2010
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25. N-myc Downstream Regulated Gene 1 (NDRG1) Is Fused to ERG in Prostate Cancer

Author

Pflueger, Dorothee, primary, Rickman, David S., additional, Sboner, Andrea, additional, Perner, Sven, additional, LaFargue, Christopher J., additional, Svensson, Maria A., additional, Moss, Benjamin J., additional, Kitabayashi, Naoki, additional, Pan, Yihang, additional, de la Taille, Alexandre, additional, Kuefer, Rainer, additional, Tewari, Ashutosh K., additional, Demichelis, Francesca, additional, Chee, Mark S., additional, Gerstein, Mark B., additional, and Rubin, Mark A., additional

Published
2009
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26. Distinct genomic aberrations associated withERGrearranged prostate cancer

Author

Demichelis, Francesca, primary, Setlur, Sunita R., additional, Beroukhim, Rameen, additional, Perner, Sven, additional, Korbel, Jan O., additional, LaFargue, Christopher J., additional, Pflueger, Dorothee, additional, Pina, Cara, additional, Hofer, Matthias D., additional, Sboner, Andrea, additional, Svensson, Maria A., additional, Rickman, David S., additional, Urban, Alex, additional, Snyder, Michael, additional, Meyerson, Matthew, additional, Lee, Charles, additional, Gerstein, Mark B., additional, Kuefer, Rainer, additional, and Rubin, Mark A., additional

Published
2009
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27. SLC45A3-ELK4 Is a Novel and Frequent Erythroblast Transformation–Specific Fusion Transcript in Prostate Cancer

Author

Rickman, David S., primary, Pflueger, Dorothee, additional, Moss, Benjamin, additional, VanDoren, Vanessa E., additional, Chen, Chen X., additional, de la Taille, Alexandre, additional, Kuefer, Rainer, additional, Tewari, Ashutosh K., additional, Setlur, Sunita R., additional, Demichelis, Francesca, additional, and Rubin, Mark A., additional

Published
2009
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28. Distinct genomic aberrations associated with ERG rearranged prostate cancer.

Author

Demichelis, Francesca, Setlur, Sunita R., Beroukhim, Rameen, Perner, Sven, Korbel, Jan O., LaFargue, Christopher J., Pflueger, Dorothee, Pina, Cara, Hofer, Matthias D., Sboner, Andrea, Svensson, Maria A., Rickman, David S., Urban, Alex, Snyder, Michael, Meyerson, Matthew, Lee, Charles, Gerstein, Mark B., Kuefer, Rainer, and Rubin, Mark A.

Published
2009
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30. Discovery of non-ETS gene fusions in human prostate cancer using next-generation RNA sequencing.

Author

Pflueger, Dorothee, Terry, St⇔(c)phane, Sboner, Andrea, Habegger, Lukas, Esgueva, Raquel, Pei-Chun Lin, Svensson, Maria A., Kitabayashi, Naoki, Moss, Benjamin J., MacDonald, Theresa Y., Xuhong Cao, Barrette, Terrence, Tewari, Ashutosh K., Chee, Mark S., Chinnaiyan, Arul M., Rickman, David S., Demichelis, Francesca, Gerstein, Mark B., and Rubin, Mark A.

Subjects
*PROSTATE cancer, *RNA, *GENE fusion, *NUCLEOTIDE sequence, *GENETIC transcription
Abstract

Half of prostate cancers harbor gene fusions between TMPRSS2 and members of the ETS transcription factor family. To date, little is known about the presence of non-ETS fusion events in prostate cancer. We used next-generation transcriptome sequencing (RNA-seq) in order to explore the whole transcriptome of 25 human prostate cancer samples for the presence of chimeric fusion transcripts. We generated more than 1 billion sequence reads and used a novel computational approach (FusionSeq) in order to identify novel gene fusion candidates with high confidence. In total, we discovered and characterized seven new cancer-specific gene fusions, two involving the ETS genes ETV1 and ERG, and four involving non-ETS genes such as CDKN1A (p21), CD9, and IKBKB (IKK-beta), genes known to exhibit key biological roles in cellular homeostasis or assumed to be critical in tumorigenesis of other tumor entities, as well as the oncogene PIGU and the tumor suppressor gene RSRC2. The novel gene fusions are found to be of low frequency, but, interestingly, the non-ETS fusions were all present in prostate cancer harboring the TMPRSS2-ERG gene fusion. Future work will focus on determining if the ETS rearrangements in prostate cancer are associated or directly predispose to a rearrangement-prone phenotype. [ABSTRACT FROM AUTHOR]

Published
2011
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31. Identification of Molecular Tumor Markers in Renal Cell Carcinomas with TFE3 Protein Expression by RNA Sequencing

Author

Jasmine Roth, Andrea Sboner, Martina Storz, Elisabeth Bruder, Eva Comperat, Peter Schraml, Mark A. Rubin, Holger Moch, Dorothee Pflueger, Competence Center for Systems Physiology and Metabolic Diseases, University hospital of Zurich [Zurich], Life Science Zürich, Weill Medical College of Cornell University [New York], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), University Hospital Basel [Basel], Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Zurich, and Pflueger, Dorothee

Subjects
Male, Cancer Research, Oncogene Proteins, Fusion, Vesicular Transport Proteins, TFE3, RNA-Seq, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Translocation, Genetic, Peptide Elongation Factor 1, 0302 clinical medicine, Gene expression, 1306 Cancer Research, Child, Aged, 80 and over, 0303 health sciences, medicine.diagnostic_test, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Middle Aged, Proto-Oncogene Proteins c-met, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Kidney Neoplasms, 3. Good health, ErbB Receptors, 030220 oncology & carcinogenesis, Female, Research Article, Adult, Adolescent, EEF1A2, 610 Medicine & health, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, lcsh:RC254-282, Young Adult, 03 medical and health sciences, Contactins, Chimeric RNA, 10049 Institute of Pathology and Molecular Pathology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Biomarkers, Tumor, medicine, Humans, Point Mutation, Carcinoma, Renal Cell, Aged, 030304 developmental biology, Sequence Analysis, RNA, Gene signature, medicine.disease, Vascular Endothelial Growth Factor Receptor-2, Molecular biology, Adaptor Proteins, Vesicular Transport, Clear cell renal cell carcinoma, Cancer research, Fluorescence in situ hybridization
Abstract

International audience; TFE3 translocation renal cell carcinoma (tRCC) is defined by chromosomal translocations involving the TFE3 transcription factor at chromosome Xp11.2. Genetically proven TFE3 tRCCs have a broad histologic spectrum with overlapping features to other renal tumor subtypes. In this study, we aimed for characterizing RCC with TFE3 protein expression. Using next-generation whole transcriptome sequencing (RNA-Seq) as a discovery tool, we analyzed fusion transcripts, gene expression profile, and somatic mutations in frozen tissue of one TFE3 tRCC. By applying a computational analysis developed to call chimeric RNA molecules from paired-end RNA-Seq data, we confirmed the known TFE3 trans-location. Its fusion partner SFPQ has already been described as fusion partner in tRCCs. In addition, an RNA read-through chimera between TMED6 and COG8 as well as MET and KDR (VEGFR2) point mutations were identified. An EGFR mutation, but no chromosomal rearrangements, was identified in a control group of five clear cell RCCs (ccRCCs). The TFE3 tRCC could be clearly distinguished from the ccRCCs by RNA-Seq gene expression measurements using a previously reported tRCC gene signature. In validation experiments using reverse transcription–PCR, TMED6-COG8 chimera expression was significantly higher in nine TFE3 translocated and six TFE3-expressing/non-translocated RCCs than in 24 ccRCCs (P < .001) and 22 papillary RCCs (P < .05-.07). Immunohistochemical analysis of selected genes from the tRCC gene signature showed significantly higher eukaryotic translation elongation factor 1 alpha 2 (EEF1A2) and Contactin 3 (CNTN3) expression in 16 TFE3 translocated and six TFE3-expressing/non-translocated RCCs than in over 200 ccRCCs (P < .0001, both).

Published
2013
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