Subclonal TP53 copy number is associated with prognosis in multiple myeloma

Publication Date:
2018-12-07
Publisher:
American Society of Hematology (ASH)
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
Medicine
Keywords:
Multiple Myeloma, Lymphoid Neoplasia, Brief Reports, Clinical Trials and Observations
Published by:
http://www.hematology.org/
_version_ 1836399099114422272
autor Shah, V., Johnson, D. C., Sherborne, A. L., Ellis, S., Aldridge, F. M., Howard-Reeves, J., Begum, F., Price, A., Kendall, J., Chiecchio, L., Savola, S., Jenner, M. W., Drayson, M. T., Owen, R. G., Gregory, W. M., Morgan, G. J., Davies, F. E., Houlston, R. S., Cook, G., Cairns, D. A., Jackson, G., Kaiser, M. F., on behalf of the National Cancer Research Institute Haematology Clinical Studies Group
beschreibung Multiple myeloma (MM) is a genetically heterogeneous cancer of bone marrow plasma cells with variable outcome. To assess the prognostic relevance of clonal heterogeneity of TP53 copy number, we profiled tumors from 1777 newly diagnosed Myeloma XI trial patients with multiplex ligation-dependent probe amplification (MLPA). Subclonal TP53 deletions were independently associated with shorter overall survival, with a hazard ratio of 1.8 (95% confidence interval, 1.2-2.8; P = .01). Clonal, but not subclonal, TP53 deletions were associated with clinical markers of advanced disease, specifically lower platelet counts ( P 〈 .001) and increased lactate dehydrogenase ( P 〈 .001), as well as a higher frequency of features indicative of genomic instability, del(13q) ( P = .002) or del(1p) ( P = .006). Biallelic TP53 loss-of-function by mutation and deletion was rare (2.4%) and associated with advanced disease. We present a framework for identifying subclonal TP53 deletions by MLPA, to improve patient stratification in MM and tailor therapy, enabling management strategies.
citation_standardnr 6365782
datenlieferant ipn_articles
feed_id 310
feed_publisher American Society of Hematology (ASH)
feed_publisher_url http://www.hematology.org/
insertion_date 2018-12-07
journaleissn 1528-0020
journalissn 0006-4971
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher American Society of Hematology (ASH)
quelle Blood
relation http://www.bloodjournal.org/cgi/content/short/132/23/2465?rss=1
schlagwort Multiple Myeloma, Lymphoid Neoplasia, Brief Reports, Clinical Trials and Observations
search_space articles
shingle_author_1 Shah, V., Johnson, D. C., Sherborne, A. L., Ellis, S., Aldridge, F. M., Howard-Reeves, J., Begum, F., Price, A., Kendall, J., Chiecchio, L., Savola, S., Jenner, M. W., Drayson, M. T., Owen, R. G., Gregory, W. M., Morgan, G. J., Davies, F. E., Houlston, R. S., Cook, G., Cairns, D. A., Jackson, G., Kaiser, M. F., on behalf of the National Cancer Research Institute Haematology Clinical Studies Group
shingle_author_2 Shah, V., Johnson, D. C., Sherborne, A. L., Ellis, S., Aldridge, F. M., Howard-Reeves, J., Begum, F., Price, A., Kendall, J., Chiecchio, L., Savola, S., Jenner, M. W., Drayson, M. T., Owen, R. G., Gregory, W. M., Morgan, G. J., Davies, F. E., Houlston, R. S., Cook, G., Cairns, D. A., Jackson, G., Kaiser, M. F., on behalf of the National Cancer Research Institute Haematology Clinical Studies Group
shingle_author_3 Shah, V., Johnson, D. C., Sherborne, A. L., Ellis, S., Aldridge, F. M., Howard-Reeves, J., Begum, F., Price, A., Kendall, J., Chiecchio, L., Savola, S., Jenner, M. W., Drayson, M. T., Owen, R. G., Gregory, W. M., Morgan, G. J., Davies, F. E., Houlston, R. S., Cook, G., Cairns, D. A., Jackson, G., Kaiser, M. F., on behalf of the National Cancer Research Institute Haematology Clinical Studies Group
shingle_author_4 Shah, V., Johnson, D. C., Sherborne, A. L., Ellis, S., Aldridge, F. M., Howard-Reeves, J., Begum, F., Price, A., Kendall, J., Chiecchio, L., Savola, S., Jenner, M. W., Drayson, M. T., Owen, R. G., Gregory, W. M., Morgan, G. J., Davies, F. E., Houlston, R. S., Cook, G., Cairns, D. A., Jackson, G., Kaiser, M. F., on behalf of the National Cancer Research Institute Haematology Clinical Studies Group
shingle_catch_all_1 Subclonal TP53 copy number is associated with prognosis in multiple myeloma
Multiple Myeloma, Lymphoid Neoplasia, Brief Reports, Clinical Trials and Observations
Multiple myeloma (MM) is a genetically heterogeneous cancer of bone marrow plasma cells with variable outcome. To assess the prognostic relevance of clonal heterogeneity of TP53 copy number, we profiled tumors from 1777 newly diagnosed Myeloma XI trial patients with multiplex ligation-dependent probe amplification (MLPA). Subclonal TP53 deletions were independently associated with shorter overall survival, with a hazard ratio of 1.8 (95% confidence interval, 1.2-2.8; P = .01). Clonal, but not subclonal, TP53 deletions were associated with clinical markers of advanced disease, specifically lower platelet counts ( P < .001) and increased lactate dehydrogenase ( P < .001), as well as a higher frequency of features indicative of genomic instability, del(13q) ( P = .002) or del(1p) ( P = .006). Biallelic TP53 loss-of-function by mutation and deletion was rare (2.4%) and associated with advanced disease. We present a framework for identifying subclonal TP53 deletions by MLPA, to improve patient stratification in MM and tailor therapy, enabling management strategies.
Shah, V., Johnson, D. C., Sherborne, A. L., Ellis, S., Aldridge, F. M., Howard-Reeves, J., Begum, F., Price, A., Kendall, J., Chiecchio, L., Savola, S., Jenner, M. W., Drayson, M. T., Owen, R. G., Gregory, W. M., Morgan, G. J., Davies, F. E., Houlston, R. S., Cook, G., Cairns, D. A., Jackson, G., Kaiser, M. F., on behalf of the National Cancer Research Institute Haematology Clinical Studies Group
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_2 Subclonal TP53 copy number is associated with prognosis in multiple myeloma
Multiple Myeloma, Lymphoid Neoplasia, Brief Reports, Clinical Trials and Observations
Multiple myeloma (MM) is a genetically heterogeneous cancer of bone marrow plasma cells with variable outcome. To assess the prognostic relevance of clonal heterogeneity of TP53 copy number, we profiled tumors from 1777 newly diagnosed Myeloma XI trial patients with multiplex ligation-dependent probe amplification (MLPA). Subclonal TP53 deletions were independently associated with shorter overall survival, with a hazard ratio of 1.8 (95% confidence interval, 1.2-2.8; P = .01). Clonal, but not subclonal, TP53 deletions were associated with clinical markers of advanced disease, specifically lower platelet counts ( P < .001) and increased lactate dehydrogenase ( P < .001), as well as a higher frequency of features indicative of genomic instability, del(13q) ( P = .002) or del(1p) ( P = .006). Biallelic TP53 loss-of-function by mutation and deletion was rare (2.4%) and associated with advanced disease. We present a framework for identifying subclonal TP53 deletions by MLPA, to improve patient stratification in MM and tailor therapy, enabling management strategies.
Shah, V., Johnson, D. C., Sherborne, A. L., Ellis, S., Aldridge, F. M., Howard-Reeves, J., Begum, F., Price, A., Kendall, J., Chiecchio, L., Savola, S., Jenner, M. W., Drayson, M. T., Owen, R. G., Gregory, W. M., Morgan, G. J., Davies, F. E., Houlston, R. S., Cook, G., Cairns, D. A., Jackson, G., Kaiser, M. F., on behalf of the National Cancer Research Institute Haematology Clinical Studies Group
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_3 Subclonal TP53 copy number is associated with prognosis in multiple myeloma
Multiple Myeloma, Lymphoid Neoplasia, Brief Reports, Clinical Trials and Observations
Multiple myeloma (MM) is a genetically heterogeneous cancer of bone marrow plasma cells with variable outcome. To assess the prognostic relevance of clonal heterogeneity of TP53 copy number, we profiled tumors from 1777 newly diagnosed Myeloma XI trial patients with multiplex ligation-dependent probe amplification (MLPA). Subclonal TP53 deletions were independently associated with shorter overall survival, with a hazard ratio of 1.8 (95% confidence interval, 1.2-2.8; P = .01). Clonal, but not subclonal, TP53 deletions were associated with clinical markers of advanced disease, specifically lower platelet counts ( P < .001) and increased lactate dehydrogenase ( P < .001), as well as a higher frequency of features indicative of genomic instability, del(13q) ( P = .002) or del(1p) ( P = .006). Biallelic TP53 loss-of-function by mutation and deletion was rare (2.4%) and associated with advanced disease. We present a framework for identifying subclonal TP53 deletions by MLPA, to improve patient stratification in MM and tailor therapy, enabling management strategies.
Shah, V., Johnson, D. C., Sherborne, A. L., Ellis, S., Aldridge, F. M., Howard-Reeves, J., Begum, F., Price, A., Kendall, J., Chiecchio, L., Savola, S., Jenner, M. W., Drayson, M. T., Owen, R. G., Gregory, W. M., Morgan, G. J., Davies, F. E., Houlston, R. S., Cook, G., Cairns, D. A., Jackson, G., Kaiser, M. F., on behalf of the National Cancer Research Institute Haematology Clinical Studies Group
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_4 Subclonal TP53 copy number is associated with prognosis in multiple myeloma
Multiple Myeloma, Lymphoid Neoplasia, Brief Reports, Clinical Trials and Observations
Multiple myeloma (MM) is a genetically heterogeneous cancer of bone marrow plasma cells with variable outcome. To assess the prognostic relevance of clonal heterogeneity of TP53 copy number, we profiled tumors from 1777 newly diagnosed Myeloma XI trial patients with multiplex ligation-dependent probe amplification (MLPA). Subclonal TP53 deletions were independently associated with shorter overall survival, with a hazard ratio of 1.8 (95% confidence interval, 1.2-2.8; P = .01). Clonal, but not subclonal, TP53 deletions were associated with clinical markers of advanced disease, specifically lower platelet counts ( P < .001) and increased lactate dehydrogenase ( P < .001), as well as a higher frequency of features indicative of genomic instability, del(13q) ( P = .002) or del(1p) ( P = .006). Biallelic TP53 loss-of-function by mutation and deletion was rare (2.4%) and associated with advanced disease. We present a framework for identifying subclonal TP53 deletions by MLPA, to improve patient stratification in MM and tailor therapy, enabling management strategies.
Shah, V., Johnson, D. C., Sherborne, A. L., Ellis, S., Aldridge, F. M., Howard-Reeves, J., Begum, F., Price, A., Kendall, J., Chiecchio, L., Savola, S., Jenner, M. W., Drayson, M. T., Owen, R. G., Gregory, W. M., Morgan, G. J., Davies, F. E., Houlston, R. S., Cook, G., Cairns, D. A., Jackson, G., Kaiser, M. F., on behalf of the National Cancer Research Institute Haematology Clinical Studies Group
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_title_1 Subclonal TP53 copy number is associated with prognosis in multiple myeloma
shingle_title_2 Subclonal TP53 copy number is associated with prognosis in multiple myeloma
shingle_title_3 Subclonal TP53 copy number is associated with prognosis in multiple myeloma
shingle_title_4 Subclonal TP53 copy number is associated with prognosis in multiple myeloma
timestamp 2025-06-30T23:37:35.338Z
titel Subclonal TP53 copy number is associated with prognosis in multiple myeloma
titel_suche Subclonal TP53 copy number is associated with prognosis in multiple myeloma
topic W
WW-YZ
uid ipn_articles_6365782