Korean J Lab Med.  2008 Dec;28(6):413-418. 10.3343/kjlm.2008.28.6.413.

Correlation of Chromosomal Aberrations with Prognostic Markers in Multiple Myeloma Patients- A Single Institution Study

• Lee JW
• Lee JK
• Hong YJ
• Hong SI
• Chang YH

• KMID: 1781574
• DOI: http://doi.org/10.3343/kjlm.2008.28.6.413

Abstract

BACKGROUND
Immunoglobulin heavy chain (IGH) gene rearrangement, 13q14 deletion and trisomy 1q are frequently observed in Korean patients with multiple myeloma. The purpose of our study was to analyze the statistical correlation between chromosomal aberrations and routine laboratory test results as prognostic markers and to evaluate the potential of chromosomal aberrations for the indirect assessment of prognosis in multiple myeloma patients.
METHODS
We investigated the prevalence of cytogenetic aberrations in 41 patients with newly diagnosed multiple myeloma. Cytogenetic analysis was conducted by conventional karyotyping and FISH for the presence of IGH/CCND1 translocation, 13q14 deletion, and trisomy 1q using bone marrow aspirates. The records of routine laboratory tests were reviewed and their correlation with cytogenetic abnormalities was investigated.
RESULTS
Sixteen (39.0%) of 41 patients had at least one cytogenetic abnormalities in conventional karyotyping or FISH. In FISH analysis of 37 patients, 8 (21.6%) showed positive result for IGH/CCND1 translocation, 8 (21.6%) for trisomy 1q, and 5 (13.5%) for 13q14 deletion. Cytogenetic abnormalities, especially trisomy 1q, were associated with significantly lower hemoglobin level and significantly higher bone marrow plasma cell percentage and beta2-microglobulin level.
CONCLUSIONS
Statistical correlation between the presence of trisomy 1q and prognostic markers suggests that the evaluation of trisomy 1q in multiple myeloma patients may be used for the indirect assessment of prognosis in these patients.

Keyword

Multiple myeloma; Cytogenetic abnormalities; Trisomy 1q

MeSH Terms

Adult
Aged
*Chromosome Aberrations
*Chromosomes, Human, Pair 1
*Chromosomes, Human, Pair 13
Female
Humans
Immunoglobulin Heavy Chains/genetics
In Situ Hybridization, Fluorescence
Karyotyping
Male
Middle Aged
Multiple Myeloma/*diagnosis/genetics
Prognosis
Translocation, Genetic
Trisomy/genetics
Tumor Markers, Biological/*blood

Reference

1.Chen L., Li J., Xu W., Qiu H., Zhu Y., Zhang Y, et al. Molecular cytogenetic aberrations in patients with multiple myeloma studied by interphase fluorescence in situ hybridization. Exp Oncol. 2007. 29:116–20.

2.Christensen JH., Abildgaard N., Plesner T., Nibe A., Nielsen O., Sorensen AG, et al. Interphase fluorescence in situ hybridization in multiple myeloma and monoclonal gammopathy of undetermined significance without and with positive plasma cell identification: analysis of 192 cases from the Region of Southern Denmark. Cancer Genet Cytogenet. 2007. 174:89–99.

3.Wu KL., Beverloo B., Lokhorst HM., Segeren CM., van der Holt B., Steijaert MM, et al. Abnormalities of chromosome 1p/q are highly associated with chromosome 13/13q deletions and are an adverse prognostic factor for the outcome of high-dose chemotherapy in patients with multiple myeloma. Br J Haematol. 2007. 136:615–23.

4.Takimoto M., Ogawa K., Kato Y., Saito T., Suzuki T., Irei M, et al. Close relation between 14q32/IGH translocations and chromosome 13 abnormalities in multiple myeloma: a high incidence of 11q13/CCND1 and 16q23/MAF. Int J Hematol. 2008. 87:260–5.

5.Hallek M., Bergsagel PL., Anderson KC. Multiple myeloma: increasing evidence for a multistep transformation process. Blood. 1998. 91:3–21.

6.Mohamed AN., Bentley G., Bonnett ML., Zonder J., Al-Katib A. Chromosome aberrations in a series of 120 multiple myeloma cases with abnormal karyotypes. Am J Hematol. 2007. 82:1080–7.

7.Chang H., Li D., Zhuang L., Nie E., Bouman D., Stewart AK, et al. Detection of chromosome 13q deletions and IgH translocations in patients with multiple myeloma by FISH: comparison with karyotype analysis. Leuk Lymphoma. 2004. 45:965–9.

8.Liebisch P., Viardot A., Bassermann N., Wendl C., Roth K., Goldschmidt H, et al. Value of comparative genomic hybridization and fluorescence in situ hybridization for molecular diagnostics in multiple myeloma. Br J Haematol. 2003. 122:193–201.

9.Liebisch P., Wendl C., Wellmann A., Krober A., Schilling G., Goldschmidt H, et al. High incidence of trisomies 1q, 9q, and 11q in multiple myeloma: results from a comprehensive molecular cytogenetic analysis. Leukemia. 2003. 17:2535–7.

10.Bang SM., Kim YR., Cho HI., Chi HS., Seo EJ., Park CJ, et al. Identification of 13q deletion, trisomy 1q, and IgH rearrangement as the most frequent chromosomal changes found in Korean patients with multiple myeloma. Cancer Genet Cytogenet. 2006. 168:124–32.

11.Kim KT., Paik JH., Lee CJ., Kim JH., Bae YZ., Seo BG, et al. Clinical significance of chromosomal abnormality in multiple myeloma. Korean J Med. 2005. 69:304–12. (김경태, 백정환, 이창재, 김진호, 배이지, 서봉근 등. 다발성골수종에서 염색체 이상의 임상적 중요성. 대한내과학회지 2005;69: 304-12.).

12.Hwang SH., Park CJ., Chi HS., Lee JH., Kim WK., Kim SH. Prognostic relevances of bone marrow features in patients with multiple myeloma. Korean J Clin Pathol. 1999. 19:8–14. (황상현, 박찬정, 지현숙, 이제환, 김우건, 김상희. 다발성 골수종 환자의 골수 소견과 예후와의 관련성. 대한임상병리학회지 1999;19: 8-14.).

13.The International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 2003. 121:749–57.

14.Durie BG., Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975. 36:842–54.

15.Huh JW., Ahn JY., Lee JH., Im SA., Seong CM., Chung WS. Detection of IgH and cyclin D1 gene rearrangement with interphase FISH in multiple myeloma. Korean J Lab Med. 2002. 22:367–71. (허정원, 안정렬, 이재훈, 임석아, 성주명, 정화순. 다발골수종환자에서간기세포 Fluorescence in situ Hybridization을 이용한 IgH과 Cyclin D1 재배열검색. 대한진단검사의학회지 2002;22: 367-71.).

16.Fonseca R., Blood EA., Oken MM., Kyle RA., Dewald GW., Bailey RJ, et al. Myeloma and the t(11;14)(q13;q32); evidence for a biologically defined unique subset of patients. Blood. 2002. 99:3735–41.

17.Moreau P., Facon T., Leleu X., Morineau N., Huyghe P., Harousseau JL, et al. Recurrent 14q32 translocations determine the prognosis of multiple myeloma, especially in patients receiving intensive chemotherapy. Blood. 2002. 100:1579–83.