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Translocation t(11;14) (q13;q32) and genomic imbalances in multi-ethnic multiple myeloma patients: a Malaysian study.

Ni IB, Ching NC, Meng CK, Zakaria Z - Hematol Rep (2012)

Bottom Line: In addition, aCGH results showed genomic imbalances in all samples analyzed.Frequent chromosomal gains were identified at regions 1q, 2q, 3p, 3q, 4p, 4q, 5q, 7q, 9q, 11q, 13q, 15q, 21q, 22q and Xq, while chromosomal losses were detected at 4q and 14q.Genes located in the chromosomal aberration regions in our study, such as NAMPT, IVNS1ABP, IRF2BP2, PICALM, STAT1, STK17B, FBXL5, ACSL1, LAMP2, SAMSN1 and ATP8B4 might be potential prognostic markers and therapeutic targets in the treatment and management of multiple myeloma patients positive for BCL1/JH t(11;14) (q13;q32) translocation.

View Article: PubMed Central - PubMed

Affiliation: Hematology Unit, Cancer Research Centre, Institute for Medical Research, Kuala Lumpur;

ABSTRACT
More than 50% of myeloma cases have normal karyotypes under conventional cytogenetic analysis due to low mitotic activity and content of plasma cells in the bone marrow. We used a polymerase chain reaction (PCR)-based translocation detection assay to detect BCL1/JH t(11;14) (q13;q32) in 105 myeloma patients, and randomly selected 8 translocation positive samples for array comparative genomic hybridization (aCGH) analysis. Our findings revealed 14.3% of myeloma samples were positive for BCL1/JH t(11;14) (q13;q32) translocation (n=15 of 105). We found no significant correlation between this translocation with age (P=0.420), gender (P=0.317), ethnicity (P=0.066) or new/relapsed status of multiple myeloma (P=0.412) at 95% confidence interval level by χ(2)test. In addition, aCGH results showed genomic imbalances in all samples analyzed. Frequent chromosomal gains were identified at regions 1q, 2q, 3p, 3q, 4p, 4q, 5q, 7q, 9q, 11q, 13q, 15q, 21q, 22q and Xq, while chromosomal losses were detected at 4q and 14q. Copy number variations at genetic loci that contain NAMPT, IVNS1ABP and STK17B genes are new findings that have not previously been reported in myeloma patients. Besides fluorescence in situ hybridization, PCR is another rapid, sensitive and simple technique that can be used for detecting BCL1/JH t(11;14)(q13;q32) translocation in multiple myeloma patients. Genes located in the chromosomal aberration regions in our study, such as NAMPT, IVNS1ABP, IRF2BP2, PICALM, STAT1, STK17B, FBXL5, ACSL1, LAMP2, SAMSN1 and ATP8B4 might be potential prognostic markers and therapeutic targets in the treatment and management of multiple myeloma patients positive for BCL1/JH t(11;14) (q13;q32) translocation.

No MeSH data available.


Related in: MedlinePlus

Polymerase chain reaction (PCR) products of 15 BCL1/JH t(11;14)(13q;32q) positive multiple myeloma patients on bioanalyzer. Each sample was performed in duplicate. PCR product size ranged between 200bp-300bp. Negative controls and samples showed a faint unspecific band at ∼600bp. No band was observed in the non-template controls and water controls indicated that there was no cross-contamination of reagent during the PCR preparation.
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Figure 1: Polymerase chain reaction (PCR) products of 15 BCL1/JH t(11;14)(13q;32q) positive multiple myeloma patients on bioanalyzer. Each sample was performed in duplicate. PCR product size ranged between 200bp-300bp. Negative controls and samples showed a faint unspecific band at ∼600bp. No band was observed in the non-template controls and water controls indicated that there was no cross-contamination of reagent during the PCR preparation.

Mentions: Our results revealed 14.3% of the myeloma samples under studied were positive for BCL1/JH t(11;14) translocation (n=15 of 105). One of the samples was derived from the relapsed MM patient (RM9) while the remaining were from newly diagnosed myeloma cases (Figure 1). Sequencing results verified that all the BCL1/JH t(11;14) translocation positive samples contained the joining sequences of MTC of the BCL1 locus and the region of the immunoglobulin heavy chain locus. Secuencing result for RM9 is illustrated in Figuer 2. χ2 analysis showed that there was no significant correlation between BCL1/JH t(11;14) translocation and patient age (P=0.420), gender (P=0.317), ethnicity (P=0.066) or new/relapsed status of MM (P=0.412) at 95% confidence interval level. Interestingly, BCL1/JH t(11;14) translocation was not detected in all samples, which showed chromosomal abnormalities from conventional cytogenetic analysis.


Translocation t(11;14) (q13;q32) and genomic imbalances in multi-ethnic multiple myeloma patients: a Malaysian study.

Ni IB, Ching NC, Meng CK, Zakaria Z - Hematol Rep (2012)

Polymerase chain reaction (PCR) products of 15 BCL1/JH t(11;14)(13q;32q) positive multiple myeloma patients on bioanalyzer. Each sample was performed in duplicate. PCR product size ranged between 200bp-300bp. Negative controls and samples showed a faint unspecific band at ∼600bp. No band was observed in the non-template controls and water controls indicated that there was no cross-contamination of reagent during the PCR preparation.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475941&req=5

Figure 1: Polymerase chain reaction (PCR) products of 15 BCL1/JH t(11;14)(13q;32q) positive multiple myeloma patients on bioanalyzer. Each sample was performed in duplicate. PCR product size ranged between 200bp-300bp. Negative controls and samples showed a faint unspecific band at ∼600bp. No band was observed in the non-template controls and water controls indicated that there was no cross-contamination of reagent during the PCR preparation.
Mentions: Our results revealed 14.3% of the myeloma samples under studied were positive for BCL1/JH t(11;14) translocation (n=15 of 105). One of the samples was derived from the relapsed MM patient (RM9) while the remaining were from newly diagnosed myeloma cases (Figure 1). Sequencing results verified that all the BCL1/JH t(11;14) translocation positive samples contained the joining sequences of MTC of the BCL1 locus and the region of the immunoglobulin heavy chain locus. Secuencing result for RM9 is illustrated in Figuer 2. χ2 analysis showed that there was no significant correlation between BCL1/JH t(11;14) translocation and patient age (P=0.420), gender (P=0.317), ethnicity (P=0.066) or new/relapsed status of MM (P=0.412) at 95% confidence interval level. Interestingly, BCL1/JH t(11;14) translocation was not detected in all samples, which showed chromosomal abnormalities from conventional cytogenetic analysis.

Bottom Line: In addition, aCGH results showed genomic imbalances in all samples analyzed.Frequent chromosomal gains were identified at regions 1q, 2q, 3p, 3q, 4p, 4q, 5q, 7q, 9q, 11q, 13q, 15q, 21q, 22q and Xq, while chromosomal losses were detected at 4q and 14q.Genes located in the chromosomal aberration regions in our study, such as NAMPT, IVNS1ABP, IRF2BP2, PICALM, STAT1, STK17B, FBXL5, ACSL1, LAMP2, SAMSN1 and ATP8B4 might be potential prognostic markers and therapeutic targets in the treatment and management of multiple myeloma patients positive for BCL1/JH t(11;14) (q13;q32) translocation.

View Article: PubMed Central - PubMed

Affiliation: Hematology Unit, Cancer Research Centre, Institute for Medical Research, Kuala Lumpur;

ABSTRACT
More than 50% of myeloma cases have normal karyotypes under conventional cytogenetic analysis due to low mitotic activity and content of plasma cells in the bone marrow. We used a polymerase chain reaction (PCR)-based translocation detection assay to detect BCL1/JH t(11;14) (q13;q32) in 105 myeloma patients, and randomly selected 8 translocation positive samples for array comparative genomic hybridization (aCGH) analysis. Our findings revealed 14.3% of myeloma samples were positive for BCL1/JH t(11;14) (q13;q32) translocation (n=15 of 105). We found no significant correlation between this translocation with age (P=0.420), gender (P=0.317), ethnicity (P=0.066) or new/relapsed status of multiple myeloma (P=0.412) at 95% confidence interval level by χ(2)test. In addition, aCGH results showed genomic imbalances in all samples analyzed. Frequent chromosomal gains were identified at regions 1q, 2q, 3p, 3q, 4p, 4q, 5q, 7q, 9q, 11q, 13q, 15q, 21q, 22q and Xq, while chromosomal losses were detected at 4q and 14q. Copy number variations at genetic loci that contain NAMPT, IVNS1ABP and STK17B genes are new findings that have not previously been reported in myeloma patients. Besides fluorescence in situ hybridization, PCR is another rapid, sensitive and simple technique that can be used for detecting BCL1/JH t(11;14)(q13;q32) translocation in multiple myeloma patients. Genes located in the chromosomal aberration regions in our study, such as NAMPT, IVNS1ABP, IRF2BP2, PICALM, STAT1, STK17B, FBXL5, ACSL1, LAMP2, SAMSN1 and ATP8B4 might be potential prognostic markers and therapeutic targets in the treatment and management of multiple myeloma patients positive for BCL1/JH t(11;14) (q13;q32) translocation.

No MeSH data available.


Related in: MedlinePlus