TY - JOUR
T1 - Jumping translocations of 1q12 in multiple myeloma
T2 - A novel mechanism for deletion of 17p in cytogenetically defined high-risk disease
AU - Sawyer, Jeffrey R.
AU - Tian, Erming
AU - Heuck, Christoph J.
AU - Epstein, Joshua
AU - Johann, Donald J.
AU - Swanson, Charles M.
AU - Lukacs, Janet L.
AU - Johnson, Marian
AU - Binz, Regina
AU - Boast, Angela
AU - Sammartino, Gael
AU - Usmani, Saad
AU - Zangari, Maurizio
AU - Waheed, Sarah
AU - Van Rhee, Frits
AU - Barlogie, Bart
PY - 2014/4/17
Y1 - 2014/4/17
N2 - Multiple myeloma (MM) is a B-cell malignancy driven in part by increasing copy number alterations (CNAs) during disease progression. Prognostically significant CNAs accumulate during clonal evolution and include gains of 1q21 and deletions of 17p, among others. Unfortunately, the mechanisms underlying the accumulation of CNAs and resulting subclonal heterogeneity in high-risk MM are poorly understood. To investigate the impact of jumping translocations of 1q12 (JT1q12) on receptor chromosomes (RCs) and subsequent clonal evolution, we analyzed specimens from 86 patients selected for unbalanced 1q12 aberrations by G-banding. Utilizing spectral karyotyping and locus-specific fluorescence in situ hybridization, we identified 10 patients with unexpected focal amplifications of an RC that subsequently translocated as part of a sequential JT1q12 to one or more additional RCs. Four patients exhibited amplification and translocation of 8q24 (MYC), 3 showed amplification of 16q11, and 1 each displayed amplification of 18q21.3 (BCL2), 18q23, or 4p16 (FGFR3). Unexpectedly, in 6 of 14 patients with the combination of the t(4;14) and deletion of 17p, we identified the loss of 17p as resulting from a JT1q12. Here, we provide evidence that the JT1q12 is a mechanism for the simultaneous gain of 1q21 and deletion of 17p in cytogenetically defined high-risk disease.
AB - Multiple myeloma (MM) is a B-cell malignancy driven in part by increasing copy number alterations (CNAs) during disease progression. Prognostically significant CNAs accumulate during clonal evolution and include gains of 1q21 and deletions of 17p, among others. Unfortunately, the mechanisms underlying the accumulation of CNAs and resulting subclonal heterogeneity in high-risk MM are poorly understood. To investigate the impact of jumping translocations of 1q12 (JT1q12) on receptor chromosomes (RCs) and subsequent clonal evolution, we analyzed specimens from 86 patients selected for unbalanced 1q12 aberrations by G-banding. Utilizing spectral karyotyping and locus-specific fluorescence in situ hybridization, we identified 10 patients with unexpected focal amplifications of an RC that subsequently translocated as part of a sequential JT1q12 to one or more additional RCs. Four patients exhibited amplification and translocation of 8q24 (MYC), 3 showed amplification of 16q11, and 1 each displayed amplification of 18q21.3 (BCL2), 18q23, or 4p16 (FGFR3). Unexpectedly, in 6 of 14 patients with the combination of the t(4;14) and deletion of 17p, we identified the loss of 17p as resulting from a JT1q12. Here, we provide evidence that the JT1q12 is a mechanism for the simultaneous gain of 1q21 and deletion of 17p in cytogenetically defined high-risk disease.
UR - http://www.scopus.com/inward/record.url?scp=84899046793&partnerID=8YFLogxK
U2 - 10.1182/blood-2013-12-546077
DO - 10.1182/blood-2013-12-546077
M3 - Article
C2 - 24497533
AN - SCOPUS:84899046793
SN - 0006-4971
VL - 123
SP - 2504
EP - 2512
JO - Blood
JF - Blood
IS - 16
ER -