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2. Supplementary Table S1 from Comparison of Biomarker Assays for EGFR: Implications for Precision Medicine in Patients with Glioblastoma

Author

Lassman, Andrew B., primary, Roberts-Rapp, Lisa, primary, Sokolova, Irina, primary, Song, Minghao, primary, Pestova, Ekaterina, primary, Kular, Rupinder, primary, Mullen, Carolyn, primary, Zha, Zheng, primary, Lu, Xin, primary, Gomez, Erica, primary, Bhathena, Anahita, primary, Maag, David, primary, Kumthekar, Priya, primary, Gan, Hui K., primary, Scott, Andrew M., primary, Guseva, Maria, primary, Holen, Kyle D., primary, Ansell, Peter J., primary, and van den Bent, Martin J., primary

Published
2023
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3. Supplemental Tables and Figures from Comparison of Biomarker Assays for EGFR: Implications for Precision Medicine in Patients with Glioblastoma

Author

Lassman, Andrew B., primary, Roberts-Rapp, Lisa, primary, Sokolova, Irina, primary, Song, Minghao, primary, Pestova, Ekaterina, primary, Kular, Rupinder, primary, Mullen, Carolyn, primary, Zha, Zheng, primary, Lu, Xin, primary, Gomez, Erica, primary, Bhathena, Anahita, primary, Maag, David, primary, Kumthekar, Priya, primary, Gan, Hui K., primary, Scott, Andrew M., primary, Guseva, Maria, primary, Holen, Kyle D., primary, Ansell, Peter J., primary, and van den Bent, Martin J., primary

Published
2023
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4. An Optimized Set of Fluorescence In Situ Hybridization Probes for Detection of Pancreatobiliary Tract Cancer in Cytology Brush Samples

Author

Barr Fritcher, Emily G., Voss, Jesse S., Brankley, Shannon M., Campion, Michael B., Jenkins, Sarah M., Keeney, Matthew E., Henry, Michael R., Kerr, Sarah M., Chaiteerakij, Roongruedee, Pestova, Ekaterina V., Clayton, Amy C., Zhang, Jun, Roberts, Lewis R., Gores, Gregory J., Halling, Kevin C., and Kipp, Benjamin R.

Published
2015
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5. Single-Cell Genetic Analysis Reveals Insights into Clonal Development of Prostate Cancers and Indicates Loss of PTEN as a Marker of Poor Prognosis

Author

Heselmeyer-Haddad, Kerstin M., Berroa Garcia, Lissa Y., Bradley, Amanda, Hernandez, Leanora, Hu, Yue, Habermann, Jens K., Dumke, Christoph, Thorns, Christoph, Perner, Sven, Pestova, Ekaterina, Burke, Catherine, Chowdhury, Salim A., Schwartz, Russell, Schäffer, Alejandro A., Paris, Pamela L., and Ried, Thomas

Published
2014
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8. Isolation and characterization of three Streptococcus pneumoniae transformation-specific loci by use of a lacZ reporter insertion vector

Author

Pestova, Ekaterina V. and Morrison, Donald A.

Subjects
Streptococcus pneumoniae -- Genetic aspects, Genetic transformation -- Research, Genetic transcription -- Research, Biological sciences
Abstract

Three Streptococcus pneumonia genetic loci were isolated and characterized. The vector pEVP3 was used to create a random lacZ transcriptional fusion. The constructs with competence-specific galactosidase production provided three insertion mutants with beta-Gal levels ranging from 4, 10 and 40 Miller units. Subcloned chromosomal loci demonstrated resemblance to the operons of Bacillus subtilis com. Genes at all three loci were found to be important components in transformation by mutagenesis using pEVP3 for insertion duplications.

Published
1998

11. Comparison of Biomarker Assays for EGFR: Implications for Precision Medicine in Patients with Glioblastoma

Author

Lassman, Andrew B., primary, Roberts-Rapp, Lisa, additional, Sokolova, Irina, additional, Song, Minghao, additional, Pestova, Ekaterina, additional, Kular, Rupinder, additional, Mullen, Carolyn, additional, Zha, Zheng, additional, Lu, Xin, additional, Gomez, Erica, additional, Bhathena, Anahita, additional, Maag, David, additional, Kumthekar, Priya, additional, Gan, Hui K., additional, Scott, Andrew M., additional, Guseva, Maria, additional, Holen, Kyle D., additional, Ansell, Peter J., additional, and van den Bent, Martin J., additional

Published
2019
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12. Additional file 1: Table S1. of Anti-c-Met monoclonal antibody ABT-700 breaks oncogene addiction in tumors with MET amplification

Author

Jieyi Wang, Goetsch, Liliane, Tucker, Lora, Zhang, Qian, Gonzalez, Alexandra, Kedar Vaidya, Oleksijew, Anatol, Boghaert, Erwin, Minghao Song, Sokolova, Irina, Pestova, Ekaterina, Anderson, Mark, Pappano, William, Ansell, Peter, Bhathena, Anahita, Naumovski, Louie, Corvaia, Nathalie, and Reilly, Edward

Abstract

Summary of tumor lines used in the study. (DOC 69 kb)

Published
2016
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13. Additional file 4: Figure S2. of Anti-c-Met monoclonal antibody ABT-700 breaks oncogene addiction in tumors with MET amplification

Author

Jieyi Wang, Goetsch, Liliane, Tucker, Lora, Zhang, Qian, Gonzalez, Alexandra, Kedar Vaidya, Oleksijew, Anatol, Boghaert, Erwin, Minghao Song, Sokolova, Irina, Pestova, Ekaterina, Anderson, Mark, Pappano, William, Ansell, Peter, Bhathena, Anahita, Naumovski, Louie, Corvaia, Nathalie, and Reilly, Edward

Subjects
heterocyclic compounds
Abstract

IHC analysis of SNU5 tumors treated with ABT-700 in dose response for 21. (PPT 1098 kb)

Published
2016
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14. Additional file 3: Figure S1. of Anti-c-Met monoclonal antibody ABT-700 breaks oncogene addiction in tumors with MET amplification

Author

Jieyi Wang, Goetsch, Liliane, Tucker, Lora, Zhang, Qian, Gonzalez, Alexandra, Kedar Vaidya, Oleksijew, Anatol, Boghaert, Erwin, Minghao Song, Sokolova, Irina, Pestova, Ekaterina, Anderson, Mark, Pappano, William, Ansell, Peter, Bhathena, Anahita, Naumovski, Louie, Corvaia, Nathalie, and Reilly, Edward

Subjects
heterocyclic compounds
Abstract

FISH images of tumor cells. These signals correspond to two target loci/centromere on chromosome homologues to which each of the fluorescent probes are bound: green, CEP7; and orange, MET. (PPT 799 kb)

Published
2016
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15. Additional file 2: of Anti-c-Met monoclonal antibody ABT-700 breaks oncogene addiction in tumors with MET amplification

Author

Jieyi Wang, Goetsch, Liliane, Tucker, Lora, Zhang, Qian, Gonzalez, Alexandra, Kedar Vaidya, Oleksijew, Anatol, Boghaert, Erwin, Minghao Song, Sokolova, Irina, Pestova, Ekaterina, Anderson, Mark, Pappano, William, Ansell, Peter, Bhathena, Anahita, Naumovski, Louie, Corvaia, Nathalie, and Reilly, Edward

Abstract

Supplementary Methods. (DOC 29 kb)

Published
2016
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18. P1.02-030 Performance Evaluation of ALK/ROS1 Dual Break Apart FISH Probe Kit (RUO) in Non-Small-Cell Lung Cancer

Author

Chang, Hyun, primary, Lim, Sun Min, additional, Kim, Hye Ryun, additional, Cha, Yoon Jin, additional, Shel, Liang, additional, Li, Gu, additional, Tai, Yan Chin, additional, Pestova, Ekaterina, additional, Polichit, Frank, additional, Perez, Thomas, additional, Soo, Ross, additional, Park, Won Young, additional, Shim, Hyo Sup, additional, and Cho, Byoung Chul, additional

Published
2017
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19. ALK FISH positivity and crizotinib efficacy in patients (pts) with non-small cell lung cancer (NSCLC).

Author

Soria, Jean-Charles, primary, Ho, Steffan N., additional, Varella-Garcia, Marileila, additional, Iafrate, A. John, additional, Solomon, Benjamin J., additional, Shaw, Alice T., additional, Blackhall, Fiona Helen, additional, Mok, Tony, additional, Wu, Yi-Long, additional, Pestova, Ekaterina, additional, Siebert, Fred W., additional, Wilner, Keith D., additional, Polli, Anna, additional, Paolini, Jolanda, additional, Lanzalone, Silvana, additional, Green, Stephanie J., additional, and Camidge, D. Ross, additional

Published
2016
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20. Anti-c-Met monoclonal antibody ABT-700 breaks oncogene addiction in tumors with MET amplification

Author

Wang, Jieyi, primary, Goetsch, Liliane, additional, Tucker, Lora, additional, Zhang, Qian, additional, Gonzalez, Alexandra, additional, Vaidya, Kedar S., additional, Oleksijew, Anatol, additional, Boghaert, Erwin, additional, Song, Minghao, additional, Sokolova, Irina, additional, Pestova, Ekaterina, additional, Anderson, Mark, additional, Pappano, William N., additional, Ansell, Peter, additional, Bhathena, Anahita, additional, Naumovski, Louie, additional, Corvaia, Nathalie, additional, and Reilly, Edward B., additional

Published
2016
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21. Mo1368 A Targeted Multicolor FISH Probe Set Increases the Diagnostic Sensitivity for Detecting Malignancy in Pancreatobiliary Brushings

Author

Barr Fritcher, Emily G., primary, Voss, Jesse S., additional, Brankley, Shannon, additional, Campion, Michael B., additional, Jenkins, Sarah M., additional, Smith, Carin Y., additional, Kerr, Sarah E., additional, Pestova, Ekaterina V., additional, Sokolova, Irina A., additional, Song, Minghao, additional, Chaiteerakij, Roongruedee, additional, Roberts, Lewis R., additional, Gores, Gregory J., additional, Halling, Kevin C., additional, and Kipp, Benjamin R., additional

Published
2015
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25. Fluorescence In-situ Hybridization (FISH) for Anaplastic Lymphoma Kinase (ALK) Gene Rearrangements on Previously Stained Routine Cytology Specimens

Author

Brankley, Shannon, primary, Henry, Michael, additional, Halling, Kevin, additional, Yi, Eunhee, additional, Minot, Douglas, additional, Voss, Jesse, additional, Pestova, Ekaterina, additional, Song, Minghao, additional, Kerr, Sarah, additional, Fritcher, Emily Barr, additional, and Kipp, Benjamin, additional

Published
2014
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28. Outcomes of Atypical Spitz Tumors With Chromosomal Copy Number Aberrations and Conventional Melanomas in Children

Author

Gerami, Pedram, primary, Cooper, Chelsea, additional, Bajaj, Shirin, additional, Wagner, Annette, additional, Fullen, Douglas, additional, Busam, Klaus, additional, Scolyer, Richard A., additional, Xu, Xiaowei, additional, Elder, David E., additional, Abraham, Ronnie M., additional, Prieto, Victor G., additional, Guitart, Joan, additional, Liu, Ping, additional, Pestova, Ekaterina, additional, and Barnhill, Raymond L., additional

Published
2013
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29. Risk Assessment for Atypical Spitzoid Melanocytic Neoplasms Using FISH to Identify Chromosomal Copy Number Aberrations

Author

Gerami, Pedram, primary, Scolyer, Richard A., additional, Xu, Xiaowei, additional, Elder, David E., additional, Abraham, Ronnie M., additional, Fullen, Douglas, additional, Prieto, Victor G., additional, LeBoit, Philip E., additional, Barnhill, Raymond L., additional, Cooper, Chelsea, additional, Yazdan, Pedram, additional, Guitart, Joan, additional, Liu, Ping, additional, Pestova, Ekaterina, additional, and Busam, Klaus, additional

Published
2013
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30. Anti-c-Met monoclonal antibody ABT-700 breaks oncogene addiction in tumors with MET amplification.

Author

Jieyi Wang, Goetsch, Liliane, Tucker, Lora, Qian Zhang, Gonzalez, Alexandra, Vaidya, Kedar S., Oleksijew, Anatol, Boghaert, Erwin, Minghao Song, Sokolova, Irina, Pestova, Ekaterina, Anderson, Mark, Pappano, William N., Ansell, Peter, Bhathena, Anahita, Naumovski, Louie, Corvaia, Nathalie, Reilly, Edward B., Wang, Jieyi, and Zhang, Qian

Subjects
MET receptor, THERAPEUTIC use of monoclonal antibodies, GENE amplification, CANCER treatment, HEPATOCYTE growth factor, ANTINEOPLASTIC agents, DRUG efficacy, HEALTH outcome assessment, ANIMALS, CELL lines, MICE, MONOCLONAL antibodies, TUMORS, PHARMACODYNAMICS
Abstract

Background: c-Met is the receptor tyrosine kinase for hepatocyte growth factor (HGF) encoded by the MET proto-oncogene. Aberrant activation of c-Met resulting from MET amplification and c-Met overexpression is associated with poor clinical outcome in multiple malignancies underscoring the importance of c-Met signaling in cancer progression. Several c-Met inhibitors have advanced to the clinic; however, the development of inhibitory c-Met-directed therapeutic antibodies has been hampered by inherent agonistic activity.Method: We generated and tested a bivalent anti-c-Met monoclonal antibody ABT-700 in vitro for binding potency and antagonistic activity and in vivo for antitumor efficacy in human tumor xenografts. Human cancer cell lines and gastric cancer tissue microarrays were examined for MET amplification by fluorescence in situ hybridization (FISH).Results: ABT-700 exhibits a distinctive ability to block both HGF-independent constitutive c-Met signaling and HGF-dependent activation of c-Met. Cancer cells addicted to the constitutively activated c-Met signaling driven by MET amplification undergo apoptosis upon exposure to ABT-700. ABT-700 induces tumor regression and tumor growth delay in preclinical tumor models of gastric and lung cancers harboring amplified MET. ABT-700 in combination with chemotherapeutics also shows additive antitumor effect. Amplification of MET in human cancer tissues can be identified by FISH.Conclusions: The preclinical attributes of ABT-700 in blocking c-Met signaling, inducing apoptosis and suppressing tumor growth in cancers with amplified MET provide rationale for examining its potential clinical utility for the treatment of cancers harboring MET amplification. [ABSTRACT FROM AUTHOR]

Published
2016
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32. Microarray-Based CGH in Cancer.

Author

Walker, John M., Roulston, Joseph E., Bartlett, John M. S., Pestova, Ekaterina, Wilber, Kim, and King, Walter

Abstract

The detection of chromosome imbalances in malignancies has been a popular and useful approach in understanding key genetic loci and the molecular pathways of carcinogenesis. Alterations in gene dosage constitutes a major mechanism that leads to an imbalance in the gene products of oncogenes or tumor suppressor genes, resulting in the loss of normal cell division. One of the more robust technologies employed for determining alterations in gene dosage has been termed "comparative genomic hybridization" (CGH). CGH is a method that measures relative DNA copy differences between hybridized test DNA labeled with one fluorophore and reference DNA labeled in a spectrally distinct fluorophore. It was developed over a decade ago by Kallioniemi et al., who applied it to the study of copy number changes, in cancer cell lines and bladder tumors (1). Two limitations of CGH technology are the inability to detect balanced changes, such as translocations and inversions, and the necessity for tumor purity (≥80%). Collectively, CGH studies done over the past decade have demonstrated that certain regions are more frequently altered. Moreover, the patterns of alterations seen in different cancers are not the same. As tumors progress, the frequency of copy number changes increase so that as much as 50% of the genome of solid tumors can be aberrant. Most of these changes are secondary effects because of the cell's inability to replicate and segregate its chromosomes in a normal fashion. [ABSTRACT FROM AUTHOR]

Published
2004
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37. Intracellular targets of moxifloxacin: a comparison with other fluoroquinolones.

Author

Pestova, Ekaterina, Millichap, John J., Noskin, Gary A., Peterson, Lance R., Pestova, E, Millichap, J J, Noskin, G A, and Peterson, L R

Subjects
ENZYME metabolism, ANTI-infective agents, COMPARATIVE studies, DRUG resistance in microorganisms, ENZYMES, RESEARCH methodology, MEDICAL cooperation, MICROBIAL sensitivity tests, GENETIC mutation, ORGANIC compounds, POLYMERASE chain reaction, QUINOLINE, QUINOLONE antibacterial agents, RESEARCH, RESERPINE, STREPTOCOCCAL diseases, STREPTOCOCCUS, EVALUATION research, SEQUENCE analysis, PHARMACODYNAMICS
Abstract

The in vitro activity of the novel 8-methoxyquinolone, moxifloxacin, against Streptococcus pneumoniae was evaluated, and the intracellular targets of this agent were studied. Analysis of mutant strains selected with moxifloxacin demonstrated that first-step mutants bore amino acid substitutions at position 81 in the GyrA subunit of DNA gyrase. This suggests that, unlike older fluoroquinolone agents such as ciprofloxacin and levofloxacin, but similar to other C-8 substituted quinolones like sparfloxacin and gatifloxacin, moxifloxacin targets the GyrA subunit of DNA gyrase as an initial lethal event. Such a mechanism results in high activity against increasingly common S. pneumoniae strains bearing substitutions in DNA topoisomerase IV. Moxifloxacin was active with an MIC of ≤ 0.25 mg/L against S. pneumoniae clinical isolates, and against mutants, selected in the laboratory with ciprofloxacin or levofloxacin, that bore a Ser-79→Phe/Tyr substitution in ParC. The moxifloxacin MIC for strains with mutations in the structural genes for both DNA gyrase subunit GyrA and DNA topoisomerase IV subunit ParC did not exceed 2 mg/L, a level within clinically achievable serum concentrations for this agent. We also found that moxifloxacin is a poor substrate for active efflux in S. pneumoniae. Therefore, the high activity of moxifloxacin against S. pneumoniae appears to be a result of both enhanced activity against DNA gyrase and topoisomerase IV, and reduced efflux from the bacterial cell. [ABSTRACT FROM PUBLISHER]

Published
2000
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38. Single-Cell Genetic Analysis Reveals Insights into Clonal Development of Prostate Cancers and Indicates Loss of PTENas a Marker of Poor Prognosis

Author

Heselmeyer-Haddad, Kerstin M., Berroa Garcia, Lissa Y., Bradley, Amanda, Hernandez, Leanora, Hu, Yue, Habermann, Jens K., Dumke, Christoph, Thorns, Christoph, Perner, Sven, Pestova, Ekaterina, Burke, Catherine, Chowdhury, Salim A., Schwartz, Russell, Schäffer, Alejandro A., Paris, Pamela L., and Ried, Thomas

Abstract

Gauging the risk of developing progressive disease is a major challenge in prostate cancer patient management. We used genetic markers to understand genomic alteration dynamics during disease progression. By using a novel, advanced, multicolor fluorescence in situhybridization approach, we enumerated copy numbers of six genes previously identified by array comparative genomic hybridization to be involved in aggressive prostate cancer [TBL1XR1, CTTNBP2, MYC(alias c-myc), PTEN, MEN1, and PDGFB] in six nonrecurrent and seven recurrent radical prostatectomy cases. An ERGbreak-apart probe to detect TMPRSS2-ERGfusions was included. Subsequent hybridization of probe panels and cell relocation resulted in signal counts for all probes in each individual cell analyzed. Differences in the degree of chromosomal and genomic instability (ie, tumor heterogeneity) or the percentage of cells with TMPRSS2-ERGfusion between samples with or without progression were not observed. Tumors from patients that progressed had more chromosomal gains and losses, and showed a higher degree of selection for a predominant clonal pattern. PTENloss was the most frequent aberration in progressers (57%), followed by TBL1XR1gain (29%). MYCgain was observed in one progresser, which was the only lesion with an ERGgain, but no TMPRSS2-ERGfusion. According to our results, a probe set consisting of PTEN, MYC, and TBL1XR1would detect progressers with 86% sensitivity and 100% specificity. This will be evaluated further in larger studies.

Published
2014
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39. A Convenient Assay for Estimating the Possible Involvement of Efflux of Fluoroquinolones by Streptococcus pneumoniaeandStaphylococcus aureus: Evidence for Diminished Moxifloxacin, Sparfloxacin, and Trovafloxacin Efflux

Author

Beyer, Rebecca, Pestova, Ekaterina, Millichap, John J., Stosor, Valentina, Noskin, Gary A., and Peterson, Lance R.

Abstract

ABSTRACTWe developed a simplified assay for estimating efflux by measuring the effect of reserpine on the growth of Streptococcus pneumoniaeand Staphylococcus aureusover 7 h. Reserpine enhanced ciprofloxacin and levofloxacin 17 to 68%. The hydrophobic drug trovafloxacin and the drug moxifloxacin, with a bulky C-7 substituent but hydrophilicity similar to that of levofloxacin, showed little (0 to 11%) reserpine-enhancing effect. The ease of resistant mutant strain selection correlated with efflux susceptibility.

Published
2000
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40. Contribution of Topoisomerase IV and DNA Gyrase Mutations in Streptococcus pneumoniaeto Resistance to Novel Fluoroquinolones

Author

Pestova, Ekaterina, Beyer, Rebecca, Cianciotto, Nicholas P., Noskin, Gary A., and Peterson, Lance R.

Abstract

ABSTRACTIn this study, we assessed the activity of ciprofloxacin, levofloxacin, sparfloxacin, and trovafloxacin against clinical isolates of Streptococcus pneumoniaethat were resistant to the less-recently developed fluoroquinolones by using defined amino acid substitutions in DNA gyrase and topoisomerase IV. The molecular basis for resistance was assessed by using mutants selected with trovafloxacin, ciprofloxacin, and levofloxacin in vitro. This demonstrated that the primary target of trovafloxacin in S. pneumoniaeis the ParC subunit of DNA topoisomerase IV, similar to most other fluoroquinolones. However, first-step mutants bearing the Ser79→Phe/Tyr substitution in topoisomerase IV subunit ParC were susceptible to trovafloxacin with a minimum inhibitory concentration of 0.25 μg/ml, and mutations in the structural genes for both topoisomerase IV subunit ParC (parC) and the DNA gyrase subunit (gyrA) were required to achieve levels of resistance above the breakpoint. The data also suggest that enhanced activity of trovafloxacin against pneumococci is due to a combination of factors that may include reduced efflux of this agent and an enhanced activity against both DNA gyrase and topoisomerase IV.

Published
1999
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41. Fluoroquinolone Resistance Is a Poor Surrogate Marker for Type II Topoisomerase Mutations in Clinical Isolates ofStreptococcus pneumoniae

Author

Millichap, John J., Pestova, Ekaterina, Siddiqui, Farida, Noskin, Gary A., and Peterson, Lance R.

Abstract

ABSTRACTThe association between fluoroquinolone susceptibility and DNA mutations coding for amino acid substitutions in the quinolone resistance-determining region was assessed with 44 clinical isolates ofStreptococcus pneumoniae. Twenty-three strains bore at least one amino acid substitution. Only seven strains with mutations were suggested by diminished susceptibility to ciprofloxacin (MIC, =2 µg/ml).

Published
2001
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42. Single-Cell Genetic Analysis Reveals Insights into Clonal Development of Prostate Cancers and Indicates Loss of PTEN as a Marker of Poor Prognosis

Author

Heselmeyer-Haddad, Kerstin M., Garcia, Lissa Y. Berroa, Bradley, Amanda, Leanora Hernandez, Hu, Yue, Habermann, Jens K., Dumke, Christoph, Thorns, Christoph, Perner, Sven, Pestova, Ekaterina, Burke, Catherine, Chowdhury, Salim A., Schwartz, Russell, Schäffer, Alejandro H., Paris, Pamela L., and Ried, Thomas

Subjects
FOS: Biological sciences, 69999 Biological Sciences not elsewhere classified, 3. Good health
Abstract

Gauging the risk of developing progressive disease is a major challenge in prostate cancer patient management. We used genetic markers to understand genomic alteration dynamics during disease progression. By using a novel, advanced, multicolor fluorescence in situ hybridization approach, we enumerated copy numbers of six genes previously identified by array comparative genomic hybridization to be involved in aggressive prostate cancer [TBL1XR1, CTTNBP2, MYC (alias c-myc), PTEN, MEN1, and PDGFB] in six nonrecurrent and seven recurrent radical prostatectomy cases. An ERG break-apart probe to detect TMPRSS2-ERG fusions was included. Subsequent hybridization of probe panels and cell relocation resulted in signal counts for all probes in each individual cell analyzed. Differences in the degree of chromosomal and genomic instability (ie, tumor heterogeneity) or the percentage of cells with TMPRSS2-ERG fusion between samples with or without progression were not observed. Tumors from patients that progressed had more chromosomal gains and losses, and showed a higher degree of selection for a predominant clonal pattern. PTEN loss was the most frequent aberration in progressers (57%), followed by TBL1XR1 gain (29%). MYC gain was observed in one progresser, which was the only lesion with an ERG gain, but no TMPRSS2-ERG fusion. According to our results, a probe set consisting of PTEN, MYC, and TBL1XR1 would detect progressers with 86% sensitivity and 100% specificity. This will be evaluated further in larger studies.

43. Single-Cell Genetic Analysis Reveals Insights into Clonal Development of Prostate Cancers and Indicates Loss of PTEN as a Marker of Poor Prognosis

Author

Heselmeyer-Haddad, Kerstin M., Garcia, Lissa Y. Berroa, Bradley, Amanda, Leanora Hernandez, Hu, Yue, Habermann, Jens K., Dumke, Christoph, Thorns, Christoph, Perner, Sven, Pestova, Ekaterina, Burke, Catherine, Chowdhury, Salim A., Schwartz, Russell, Schäffer, Alejandro H., Paris, Pamela L., and Ried, Thomas

Subjects
FOS: Biological sciences, 69999 Biological Sciences not elsewhere classified, 3. Good health
Abstract

Gauging the risk of developing progressive disease is a major challenge in prostate cancer patient management. We used genetic markers to understand genomic alteration dynamics during disease progression. By using a novel, advanced, multicolor fluorescence in situ hybridization approach, we enumerated copy numbers of six genes previously identified by array comparative genomic hybridization to be involved in aggressive prostate cancer [TBL1XR1, CTTNBP2, MYC (alias c-myc), PTEN, MEN1, and PDGFB] in six nonrecurrent and seven recurrent radical prostatectomy cases. An ERG break-apart probe to detect TMPRSS2-ERG fusions was included. Subsequent hybridization of probe panels and cell relocation resulted in signal counts for all probes in each individual cell analyzed. Differences in the degree of chromosomal and genomic instability (ie, tumor heterogeneity) or the percentage of cells with TMPRSS2-ERG fusion between samples with or without progression were not observed. Tumors from patients that progressed had more chromosomal gains and losses, and showed a higher degree of selection for a predominant clonal pattern. PTEN loss was the most frequent aberration in progressers (57%), followed by TBL1XR1 gain (29%). MYC gain was observed in one progresser, which was the only lesion with an ERG gain, but no TMPRSS2-ERG fusion. According to our results, a probe set consisting of PTEN, MYC, and TBL1XR1 would detect progressers with 86% sensitivity and 100% specificity. This will be evaluated further in larger studies.

44. Microarray-based CGH in cancer.

Author

Pestova E, Wilber K, and King W

Subjects
Humans, DNA, Complementary analysis, DNA, Neoplasm analysis, Neoplasms genetics, Nucleic Acid Hybridization methods, Oligonucleotide Array Sequence Analysis methods
Published
2004
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