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Identification of characteristic and prognostic values of chromosome 1p abnormality by multi-gene fluorescence in situ hybridization in multiple myeloma

Leukemia volume 30, pages 1197–1201 (2016)Cite this article

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Cytogenetic abnormalities have been recognized as the most important prognostic factors and as an effective approach for determining the stage of disease and providing guidance for therapeutic strategies in patients with multiple myeloma (MM).1, 2 However, current factors based on only del(17p), t(4;14) and t(14;16) cannot completely explain the heterogeneity in this disease. Recently, extensive use of high-throughput genetic analysis tools such as global gene expression profiling and single-nucleotide polymorphism-based mapping array combined with bioinformatics and biostatistics has uncovered a plethora of prognosis-related genetic abnormalities in MM.3, 4, 5 Of these, chromosome 1p deletion (18–38% in MM) is one of the most frequent genetic abnormalities and has attracted increasing clinical interest. Chromosome 1p deletion is associated with poor outcome in myeloma patients.6, 7 Moreover, in several studies, the deletions of 1p21, 1p22 and 1p32 detected by fluorescence in situ hybridization (FISH) have been validated as independent negative prognostic factors.8, 9, 10, 11, 12 However, it remains controversial which of these genetic deletions can best predict clinical outcome due to lack of comparison of FISH data in different clinical samples, and the characteristics of chromosome 1p abnormalities remain elusive.2 Here we employed a four-color interphase FISH technique at a single-cell level, which is rarely used in previous studies. This technique also allowed analysis of compound deletions in chromosome 1p, thus providing more detailed insights of chromosome 1p abnormality as a prognostic factor.

As reported by Walker et al.13 and a 70-gene (or 17-gene) model from Arkansas,3 the four minimal common deletion regions in chromosome 1 are 1p32.3, 1p31.3, 1p22.1-1p21.3 and 1p12. Four genes, FAM46C, AHCYL1, CDC14A and CDKN2C, located in 1p12, 1p13.3, 1p21.2 and 1p32.3 were chosen to represent the four regions, respectively. FISH probes against the four genes were labeled with PromoFluor-505-aadUTP (green), PromoFluor-555-aadUTP (orange), PromoFluor-590-aadUTP (red) and PromoFluor-415-aadUTP (blue), respectively. The four-color FISH was performed in a series of patients with different stages of plasma cell dyscrasias, including 266 newly diagnosed patients, 90 with relapsed MM, 8 with secondary plasma cell leukemia and 8 with monoclonal gammopathy of undetermined significance. A total of 128 and 138 patients, respectively, received thalidomide- and bortezomib-based induction treatment as previously described.14 The clinical characteristics of the 266 newly diagnosed patients (Supplementary Table 1) and detailed methods are described in the Supplementary Material.

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (81172255, 81360353, 81400150), Science and Technology Infrastructure Program of Tianjin (12ZCDZSY17600), the Ministry of Science and Technology of China (2010DFB30270), Science Fund for Creative Research Groups (81421002), the Science and Technology Support Program of Jiangxi province (20141BBG70028), Science and Technology Cooperation Program (20151BDH80043) and Young Scientist Training Program (20153BCB23040) of Jiangxi Province. Supplementary Information accompanies this paper on the Leukemia website (http://www.nature.com/leu).

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Authors and Affiliations

  1. State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China

    F Li, L Hu, Y Xu, Z Li, S Yi, C Li, M Hao, K Ru, W Yuan, T Cheng & L Qiu

  2. Department of Hematology, The First Affiliated Hospital of Nanchang University, NanChang, China

    F Li

  3. Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA

    Z Gu & F Zhan

  4. Clinical Pathology Department of Karolinska Hospital, Karolinska Institute, Solna, Sweden

    A Zetterberg

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Li, F., Hu, L., Xu, Y. et al. Identification of characteristic and prognostic values of chromosome 1p abnormality by multi-gene fluorescence in situ hybridization in multiple myeloma. Leukemia 30, 1197–1201 (2016). https://doi.org/10.1038/leu.2015.254

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