Correlation between array-comparative genomic hybridization-defined genomic gains and losses and survival: identification of 1p31-32 deletion as a prognostic factor in myeloma

• Published in: Leukemia Vol. 24; no. 4; pp. 833 - 842
• Main Authors: CHNG, W. J, GERTZ, M. A, CHUNG, T.-H, VAN WIER, S, KEATS, J. J, BAKER, A, BERGSAGEL, P. L, CARPTEN, J, FONSECA, R
• Format: Journal Article
• Language: English
• Published: Avenel, NJ Nature Publishing Group 01.04.2010
• Subjects: Abnormalities; Antineoplastic Combined Chemotherapy Protocols; Arrays; Autografts; Biological and medical sciences; Biomarkers, Tumor - genetics; Care and treatment; Chromosome Aberrations; Chromosomes, Human, Pair 1 - genetics; Chromosomes, Human, Pair 20 - genetics; Cohort Studies; Comparative Genomic Hybridization; Dosage and administration; Fluorescence; Fluorescence in situ hybridization; Genetic aspects; Genomics; Hematologic and hematopoietic diseases; Hematopoietic Stem Cell Transplantation; Humans; Hybridization; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Impact analysis; In Situ Hybridization, Fluorescence; Karyotyping; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical prognosis; Medical sciences; Melphalan; Multiple myeloma; Multiple Myeloma - diagnosis; Multiple Myeloma - genetics; Multiple Myeloma - mortality; Multivariate analysis; Myeloma; Oligonucleotide Array Sequence Analysis; Prognosis; Stem cell transplantation; Stem cells; Survival; Survival Rate; Transplantation; United States; Immunopathology; Prognosis; Hematology; Chromosome A1; B cell neoplasm; Malignant hemopathy; Lymphoid neoplasm; Gene expression; Myeloma; Survival; Immunoglobulinopathy; Comparative genomic hybridization; Lymphoproliferative syndrome; chromosome 1p; Deletion; Genetics; array-comparative genomic hybridization; Genome; Cancer
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2010.21

In this study, we correlated array-comparative genomic hybridization-defined abnormalities with survival in two different cohorts of patients treated with therapy based on high-dose melphalan with autologous stem-cell transplantation (64 from the Mayo Clinic and 67 from the University of Arkansas Medical School) and identified that several regions of genomic gains and losses were significantly associated with poorer survival. Three noncontiguous survival relevant regions covering 1p31-33 and two noncontiguous regions covering 20p12.3-12.1 were common between the two datasets. The prognostic relevance of these hotspots was validated in an independent cohort using fluorescent in situ hybridization, which showed that 1p31-32 loss is significantly associated with shorter survival (24.5 months versus 40 months, log-rank P-value=0.01), whereas 20p12 loss has a trend toward shorter survival (26.3 months versus 40 months, log-rank P-value=0.06). On multivariate analysis, 1p31-32 loss is an independent prognostic factor. On further analysis, the prognostic impact of 1p31-32 loss is due to shortening of post-relapse survival as there is no impact on complete response rates and progression-free survival.