TY - JOUR
T1 - Genome-wide high density single-nucleotide polymorphism array-based karyotyping improves detection of clonal aberrations including der(9) deletion, but does not predict treatment outcomes after imatinib therapy in chronic myeloid leukemia
AU - Huh, Jungwon
AU - Jung, Chul Won
AU - Kim, Jong Won
AU - Kim, Hee Jin
AU - Kim, Sun Hee
AU - Shin, Myung Geun
AU - Kim, Yeo Kyeoung
AU - Kim, Hyeoung Joon
AU - Suh, Jang Soo
AU - Moon, Joon Ho
AU - Sohn, Sang Kyung
AU - Nam, Goong Hyun
AU - Lee, Jong Eun
AU - Kim, Dong Hwan Dennis
N1 - Funding Information:
Acknowledgment This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2010–0010208), by grant from IN-SUNG Foundation for Medical Research, Samsung Medical Center, and by a grant of the Korea Healthcare technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A092255).
PY - 2011/11
Y1 - 2011/11
N2 - The current study investigated molecular cytogenetic characteristics of chronic myeloid leukemia (CML) using genome-wide, single nucleotide polymorphism arrays (SNP-A) capable of detecting cryptic submicroscopic genomic aberrations. Genome-Wide Human SNP 6.0 Array (Affymetrix, CA, USA) was performed in 118 patients having CML, chronic phase. Thirty-nine clonal aberrations (CAs) were identified (35 losses, two gains, two copy neutral loss of heterozygosity) that were not detected by metaphase cytogenetics in 25 patients (21%). The 9q34 deletions were found in 10% of cases, while 22q11.2 deletions were observed in 12% of cases. Seven patients (6%) harbored both 5'-ABL and 3'-BCR deletions adjacent to the t(9;22) breakpoint. Copy number gains were identified at 8p and 9p, and losses at 2q, 7q, 8q, 9q, 11q, 13q, 16p, and 22q. When we compared the treatment outcome of imatinib therapy between patients with and without CAs identified by SNP-A, treatment failure and progression to advanced disease were not significantly different (p>0.05). In addition, according to the presence of deletions of 9q34 and/or 22q11.2 identified by SNP-A, the treatment outcome did not show any significant differences (p>0.05). Our data suggests that SNP-A analysis is a useful tool for detection of clonal aberrations including deletions adjacent to the t(9;22) breakpoint in the CML cancer genome. However, clonal aberrations detected by SNP-A could not improve a prognostic stratification in CML patients with chronic phase.
AB - The current study investigated molecular cytogenetic characteristics of chronic myeloid leukemia (CML) using genome-wide, single nucleotide polymorphism arrays (SNP-A) capable of detecting cryptic submicroscopic genomic aberrations. Genome-Wide Human SNP 6.0 Array (Affymetrix, CA, USA) was performed in 118 patients having CML, chronic phase. Thirty-nine clonal aberrations (CAs) were identified (35 losses, two gains, two copy neutral loss of heterozygosity) that were not detected by metaphase cytogenetics in 25 patients (21%). The 9q34 deletions were found in 10% of cases, while 22q11.2 deletions were observed in 12% of cases. Seven patients (6%) harbored both 5'-ABL and 3'-BCR deletions adjacent to the t(9;22) breakpoint. Copy number gains were identified at 8p and 9p, and losses at 2q, 7q, 8q, 9q, 11q, 13q, 16p, and 22q. When we compared the treatment outcome of imatinib therapy between patients with and without CAs identified by SNP-A, treatment failure and progression to advanced disease were not significantly different (p>0.05). In addition, according to the presence of deletions of 9q34 and/or 22q11.2 identified by SNP-A, the treatment outcome did not show any significant differences (p>0.05). Our data suggests that SNP-A analysis is a useful tool for detection of clonal aberrations including deletions adjacent to the t(9;22) breakpoint in the CML cancer genome. However, clonal aberrations detected by SNP-A could not improve a prognostic stratification in CML patients with chronic phase.
KW - Chronic myeloid leukemia
KW - Copy neutral loss of heterozygosity (CN-LOH)
KW - Copy number alterations
KW - Karyotyping
KW - SNP array
UR - http://www.scopus.com/inward/record.url?scp=84855203185&partnerID=8YFLogxK
U2 - 10.1007/s00277-011-1195-2
DO - 10.1007/s00277-011-1195-2
M3 - Article
C2 - 21384125
AN - SCOPUS:84855203185
SN - 0939-5555
VL - 90
SP - 1255
EP - 1264
JO - Annals of Hematology
JF - Annals of Hematology
IS - 11
ER -