Amplification of 1q21 and Other Abnormalities in Multiple Myeloma Patients from a Tertiary Hospital in Singapore

Abstract

Much effort has been made to stratify multiple myeloma patients for targeted therapy. However, responses have been varied and improved patient stratifications are needed. Forty-five diagnostic samples from multiple myeloma patients (median age 65 years) were stratified cytogenetically as 15 having non-hyperdiploidy, 20 having hyperdiploidy and 10 having a normal karyotype. Fluorescence in situ hybridization (FISH) assays with FGFR3/IGH, CCND1/IGH, IGH/MAF, RB1 and TP53 probes on bone marrow samples showed that IGH rearrangements were the most common abnormality in the non-hyperdiploid group but these were also found among hyperdiploid patients and patients with normal cytogenetics. Of these, FGFR3/IGH rearrangements were most frequent. Deletion of RB1/ monosomy 13 was the most common genetic abnormality across the three groups and was significantly higher among non-hyperdiploid compared to hyperdiploid patients. On the other hand, the study recorded a low incidence of TP53 deletion/monosomy 17. The FGFR3/IGH fusion was frequently seen with RB1 deletion/monosomy 13. FISH with 1p36/1q21 and 6q21/15q22 probes showed that amplification of 15q22 was seen in all of the hyperdiploid patients while amplification of 1q21, Amp(1q21), characterized nonhyperdiploid patients. In contrast, deletions of 1p36 and 6q21 were very rare events. Amp(1q21), FGFR3/IGH fusion, RB1 deletion/monosomy 13, and even TP53 deletion/monosomy 17 were seen in some hyperdiploid patients, suggesting that they have a less than favorable prognosis and require closer monitoring.

Cytogenetic abnormality in patients with multiple myeloma analyzed by fluorescent in situ hybridization

“…In our study, 14q32 amplification/deletion was observed in 72.7% of patients, and t(4;14) was the most common aberration. Lim et al 4 reported that IGH rearrangements were the most common abnormality. t(4p16.3/14q32) rearrangements were most frequent.…”

1q21 Gain Combined with High-Risk Factors Is a Heterogeneous Prognostic Factor in Newly Diagnosed Multiple Myeloma: A Multicenter Study in China

“…1q21 gain is one of the most common chromosomal aberrations in MM, especially in nonwhite patients . 1q21 gain is detected in 30% to 50% of patients with NDMM .…”

Biological research on the occurrence and development of multiple myeloma and its treatment

“…The patients can be roughly divided into two categories according to chromosomal structure and numerical abnormalities: hyperdiploid and non‐hyperdiploid. 12 Odd chromosome trisomy usually occurs in hyperdiploids, mainly including +3, +5, +7, +9, +11, +15, +19, and +21. 13 Non‐hyperdiploid genes are often associated with translocations between IgH genes and other chromosomes.…”

“…Cytogenetic abnormality is one of the main basis for risk stratification of MM. The patients can be roughly divided into two categories according to chromosomal structure and numerical abnormalities: hyperdiploid and non‐hyperdiploid 12 . Odd chromosome trisomy usually occurs in hyperdiploids, mainly including +3, +5, +7, +9, +11, +15, +19, and +21 13 .…”