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Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK...
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Zeitschriftentitel: | Cancer |
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Personen und Körperschaften: | , , , , , , , , |
In: | Cancer, 118, 2012, 18, S. 4486-4494 |
Format: | E-Article |
Sprache: | Englisch |
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Wiley
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author_facet |
Camidge, D. Ross Theodoro, Mariana Maxson, DeLee A. Skokan, Margaret O'Brien, Tara Lu, Xian Doebele, Robert C. Barón, Anna E. Varella‐Garcia, Marileila Camidge, D. Ross Theodoro, Mariana Maxson, DeLee A. Skokan, Margaret O'Brien, Tara Lu, Xian Doebele, Robert C. Barón, Anna E. Varella‐Garcia, Marileila |
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author |
Camidge, D. Ross Theodoro, Mariana Maxson, DeLee A. Skokan, Margaret O'Brien, Tara Lu, Xian Doebele, Robert C. Barón, Anna E. Varella‐Garcia, Marileila |
spellingShingle |
Camidge, D. Ross Theodoro, Mariana Maxson, DeLee A. Skokan, Margaret O'Brien, Tara Lu, Xian Doebele, Robert C. Barón, Anna E. Varella‐Garcia, Marileila Cancer Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization–positive nonsmall cell lung cancer Cancer Research Oncology |
author_sort |
camidge, d. ross |
spelling |
Camidge, D. Ross Theodoro, Mariana Maxson, DeLee A. Skokan, Margaret O'Brien, Tara Lu, Xian Doebele, Robert C. Barón, Anna E. Varella‐Garcia, Marileila 0008-543X 1097-0142 Wiley Cancer Research Oncology http://dx.doi.org/10.1002/cncr.27411 <jats:title>Abstract</jats:title><jats:sec><jats:title>BACKGROUND:</jats:title><jats:p>Fluorescence in situ hybridization (FISH), using break‐apart red (3′) and green (5′) <jats:italic>ALK</jats:italic> (anaplastic lymphoma kinase) probes, consistently shows rearrangements in <100% of tumor cells in <jats:italic>ALK</jats:italic>‐positive (<jats:italic>ALK</jats:italic>+) nonsmall cell lung cancer (NSCLC). Increased copy numbers of fused and rearranged signals also occur. Here, correlations are explored between the percentage of <jats:italic>ALK</jats:italic>+ cells and signal copy number and their association with response to ALK inhibition.</jats:p></jats:sec><jats:sec><jats:title>METHODS:</jats:title><jats:p>Ninety <jats:italic>ALK</jats:italic>+ NSCLC cases were evaluated. The percentage of positive cells, pattern of positivity (split, single red, or both), and copy number of fused, isolated red and green signals were recorded. Thirty patients had received crizotinib.</jats:p></jats:sec><jats:sec><jats:title>RESULTS:</jats:title><jats:p>Increased isolated red signal copy number (contributing to both single red and split patterns of positivity) correlated with a higher percentage of <jats:italic>ALK</jats:italic>+ cells (r = 0.743, <jats:italic>P</jats:italic> < .0001). Mean fused copy number was negatively associated with isolated red signal copy number (r = −0.409, <jats:italic>P</jats:italic> < .0001). Neither percentage of positive cells (r = 0.192, <jats:italic>P</jats:italic> = .3), nor copy number of isolated red signal (r = 0.274, <jats:italic>P</jats:italic> = .195) correlated with maximal tumor shrinkage with crizotinib.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS:</jats:title><jats:p>The strong association between increased copy number of key <jats:italic>ALK</jats:italic> signals and percentage of positive cells suggests that the <100% rate of cellular positivity in <jats:italic>ALK</jats:italic>+ tumors is due to technical factors, not biological factors. In <jats:italic>ALK</jats:italic>+ tumors, neither the percentage of positive cells nor signal copy number appear to be informative variables for predicting benefit from ALK inhibition. The inverse relationship between fused and isolated red copy number suggests <jats:italic>ALK</jats:italic>+ may be a distinct “near‐diploid” subtype of NSCLC that develops before significant chromosomal aneusomy occurs. Cancer 2012. © 2012 American Cancer Society.</jats:p></jats:sec> Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (<i>ALK</i>) gene rearrangement, <i>ALK</i> signal copy number, and response to crizotinib therapy in <i>ALK</i> fluorescence in situ hybridization–positive nonsmall cell lung cancer Cancer |
doi_str_mv |
10.1002/cncr.27411 |
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Online Free |
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Medizin |
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DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 |
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Wiley, 2012 |
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Wiley, 2012 |
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0008-543X 1097-0142 |
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camidge2012correlationsbetweenthepercentageoftumorcellsshowingananaplasticlymphomakinasealkgenerearrangementalksignalcopynumberandresponsetocrizotinibtherapyinalkfluorescenceinsituhybridizationpositivenonsmallcelllungcancer |
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2012 |
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Wiley |
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Cancer |
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49 |
title |
Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization–positive nonsmall cell lung cancer |
title_unstemmed |
Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization–positive nonsmall cell lung cancer |
title_full |
Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization–positive nonsmall cell lung cancer |
title_fullStr |
Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization–positive nonsmall cell lung cancer |
title_full_unstemmed |
Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization–positive nonsmall cell lung cancer |
title_short |
Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization–positive nonsmall cell lung cancer |
title_sort |
correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (<i>alk</i>) gene rearrangement, <i>alk</i> signal copy number, and response to crizotinib therapy in <i>alk</i> fluorescence in situ hybridization–positive nonsmall cell lung cancer |
topic |
Cancer Research Oncology |
url |
http://dx.doi.org/10.1002/cncr.27411 |
publishDate |
2012 |
physical |
4486-4494 |
description |
<jats:title>Abstract</jats:title><jats:sec><jats:title>BACKGROUND:</jats:title><jats:p>Fluorescence in situ hybridization (FISH), using break‐apart red (3′) and green (5′) <jats:italic>ALK</jats:italic> (anaplastic lymphoma kinase) probes, consistently shows rearrangements in <100% of tumor cells in <jats:italic>ALK</jats:italic>‐positive (<jats:italic>ALK</jats:italic>+) nonsmall cell lung cancer (NSCLC). Increased copy numbers of fused and rearranged signals also occur. Here, correlations are explored between the percentage of <jats:italic>ALK</jats:italic>+ cells and signal copy number and their association with response to ALK inhibition.</jats:p></jats:sec><jats:sec><jats:title>METHODS:</jats:title><jats:p>Ninety <jats:italic>ALK</jats:italic>+ NSCLC cases were evaluated. The percentage of positive cells, pattern of positivity (split, single red, or both), and copy number of fused, isolated red and green signals were recorded. Thirty patients had received crizotinib.</jats:p></jats:sec><jats:sec><jats:title>RESULTS:</jats:title><jats:p>Increased isolated red signal copy number (contributing to both single red and split patterns of positivity) correlated with a higher percentage of <jats:italic>ALK</jats:italic>+ cells (r = 0.743, <jats:italic>P</jats:italic> < .0001). Mean fused copy number was negatively associated with isolated red signal copy number (r = −0.409, <jats:italic>P</jats:italic> < .0001). Neither percentage of positive cells (r = 0.192, <jats:italic>P</jats:italic> = .3), nor copy number of isolated red signal (r = 0.274, <jats:italic>P</jats:italic> = .195) correlated with maximal tumor shrinkage with crizotinib.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS:</jats:title><jats:p>The strong association between increased copy number of key <jats:italic>ALK</jats:italic> signals and percentage of positive cells suggests that the <100% rate of cellular positivity in <jats:italic>ALK</jats:italic>+ tumors is due to technical factors, not biological factors. In <jats:italic>ALK</jats:italic>+ tumors, neither the percentage of positive cells nor signal copy number appear to be informative variables for predicting benefit from ALK inhibition. The inverse relationship between fused and isolated red copy number suggests <jats:italic>ALK</jats:italic>+ may be a distinct “near‐diploid” subtype of NSCLC that develops before significant chromosomal aneusomy occurs. Cancer 2012. © 2012 American Cancer Society.</jats:p></jats:sec> |
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author | Camidge, D. Ross, Theodoro, Mariana, Maxson, DeLee A., Skokan, Margaret, O'Brien, Tara, Lu, Xian, Doebele, Robert C., Barón, Anna E., Varella‐Garcia, Marileila |
author_facet | Camidge, D. Ross, Theodoro, Mariana, Maxson, DeLee A., Skokan, Margaret, O'Brien, Tara, Lu, Xian, Doebele, Robert C., Barón, Anna E., Varella‐Garcia, Marileila, Camidge, D. Ross, Theodoro, Mariana, Maxson, DeLee A., Skokan, Margaret, O'Brien, Tara, Lu, Xian, Doebele, Robert C., Barón, Anna E., Varella‐Garcia, Marileila |
author_sort | camidge, d. ross |
container_issue | 18 |
container_start_page | 4486 |
container_title | Cancer |
container_volume | 118 |
description | <jats:title>Abstract</jats:title><jats:sec><jats:title>BACKGROUND:</jats:title><jats:p>Fluorescence in situ hybridization (FISH), using break‐apart red (3′) and green (5′) <jats:italic>ALK</jats:italic> (anaplastic lymphoma kinase) probes, consistently shows rearrangements in <100% of tumor cells in <jats:italic>ALK</jats:italic>‐positive (<jats:italic>ALK</jats:italic>+) nonsmall cell lung cancer (NSCLC). Increased copy numbers of fused and rearranged signals also occur. Here, correlations are explored between the percentage of <jats:italic>ALK</jats:italic>+ cells and signal copy number and their association with response to ALK inhibition.</jats:p></jats:sec><jats:sec><jats:title>METHODS:</jats:title><jats:p>Ninety <jats:italic>ALK</jats:italic>+ NSCLC cases were evaluated. The percentage of positive cells, pattern of positivity (split, single red, or both), and copy number of fused, isolated red and green signals were recorded. Thirty patients had received crizotinib.</jats:p></jats:sec><jats:sec><jats:title>RESULTS:</jats:title><jats:p>Increased isolated red signal copy number (contributing to both single red and split patterns of positivity) correlated with a higher percentage of <jats:italic>ALK</jats:italic>+ cells (r = 0.743, <jats:italic>P</jats:italic> < .0001). Mean fused copy number was negatively associated with isolated red signal copy number (r = −0.409, <jats:italic>P</jats:italic> < .0001). Neither percentage of positive cells (r = 0.192, <jats:italic>P</jats:italic> = .3), nor copy number of isolated red signal (r = 0.274, <jats:italic>P</jats:italic> = .195) correlated with maximal tumor shrinkage with crizotinib.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS:</jats:title><jats:p>The strong association between increased copy number of key <jats:italic>ALK</jats:italic> signals and percentage of positive cells suggests that the <100% rate of cellular positivity in <jats:italic>ALK</jats:italic>+ tumors is due to technical factors, not biological factors. In <jats:italic>ALK</jats:italic>+ tumors, neither the percentage of positive cells nor signal copy number appear to be informative variables for predicting benefit from ALK inhibition. The inverse relationship between fused and isolated red copy number suggests <jats:italic>ALK</jats:italic>+ may be a distinct “near‐diploid” subtype of NSCLC that develops before significant chromosomal aneusomy occurs. Cancer 2012. © 2012 American Cancer Society.</jats:p></jats:sec> |
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imprint | Wiley, 2012 |
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institution | DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229 |
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mega_collection | Wiley (CrossRef) |
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spelling | Camidge, D. Ross Theodoro, Mariana Maxson, DeLee A. Skokan, Margaret O'Brien, Tara Lu, Xian Doebele, Robert C. Barón, Anna E. Varella‐Garcia, Marileila 0008-543X 1097-0142 Wiley Cancer Research Oncology http://dx.doi.org/10.1002/cncr.27411 <jats:title>Abstract</jats:title><jats:sec><jats:title>BACKGROUND:</jats:title><jats:p>Fluorescence in situ hybridization (FISH), using break‐apart red (3′) and green (5′) <jats:italic>ALK</jats:italic> (anaplastic lymphoma kinase) probes, consistently shows rearrangements in <100% of tumor cells in <jats:italic>ALK</jats:italic>‐positive (<jats:italic>ALK</jats:italic>+) nonsmall cell lung cancer (NSCLC). Increased copy numbers of fused and rearranged signals also occur. Here, correlations are explored between the percentage of <jats:italic>ALK</jats:italic>+ cells and signal copy number and their association with response to ALK inhibition.</jats:p></jats:sec><jats:sec><jats:title>METHODS:</jats:title><jats:p>Ninety <jats:italic>ALK</jats:italic>+ NSCLC cases were evaluated. The percentage of positive cells, pattern of positivity (split, single red, or both), and copy number of fused, isolated red and green signals were recorded. Thirty patients had received crizotinib.</jats:p></jats:sec><jats:sec><jats:title>RESULTS:</jats:title><jats:p>Increased isolated red signal copy number (contributing to both single red and split patterns of positivity) correlated with a higher percentage of <jats:italic>ALK</jats:italic>+ cells (r = 0.743, <jats:italic>P</jats:italic> < .0001). Mean fused copy number was negatively associated with isolated red signal copy number (r = −0.409, <jats:italic>P</jats:italic> < .0001). Neither percentage of positive cells (r = 0.192, <jats:italic>P</jats:italic> = .3), nor copy number of isolated red signal (r = 0.274, <jats:italic>P</jats:italic> = .195) correlated with maximal tumor shrinkage with crizotinib.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS:</jats:title><jats:p>The strong association between increased copy number of key <jats:italic>ALK</jats:italic> signals and percentage of positive cells suggests that the <100% rate of cellular positivity in <jats:italic>ALK</jats:italic>+ tumors is due to technical factors, not biological factors. In <jats:italic>ALK</jats:italic>+ tumors, neither the percentage of positive cells nor signal copy number appear to be informative variables for predicting benefit from ALK inhibition. The inverse relationship between fused and isolated red copy number suggests <jats:italic>ALK</jats:italic>+ may be a distinct “near‐diploid” subtype of NSCLC that develops before significant chromosomal aneusomy occurs. Cancer 2012. © 2012 American Cancer Society.</jats:p></jats:sec> Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (<i>ALK</i>) gene rearrangement, <i>ALK</i> signal copy number, and response to crizotinib therapy in <i>ALK</i> fluorescence in situ hybridization–positive nonsmall cell lung cancer Cancer |
spellingShingle | Camidge, D. Ross, Theodoro, Mariana, Maxson, DeLee A., Skokan, Margaret, O'Brien, Tara, Lu, Xian, Doebele, Robert C., Barón, Anna E., Varella‐Garcia, Marileila, Cancer, Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization–positive nonsmall cell lung cancer, Cancer Research, Oncology |
title | Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization–positive nonsmall cell lung cancer |
title_full | Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization–positive nonsmall cell lung cancer |
title_fullStr | Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization–positive nonsmall cell lung cancer |
title_full_unstemmed | Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization–positive nonsmall cell lung cancer |
title_short | Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization–positive nonsmall cell lung cancer |
title_sort | correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (<i>alk</i>) gene rearrangement, <i>alk</i> signal copy number, and response to crizotinib therapy in <i>alk</i> fluorescence in situ hybridization–positive nonsmall cell lung cancer |
title_unstemmed | Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization–positive nonsmall cell lung cancer |
topic | Cancer Research, Oncology |
url | http://dx.doi.org/10.1002/cncr.27411 |