Clonal heterogeneity of lymphoid malignancies correlates with poor prognosis |
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| Authors: | Miyuki Suguro Noriaki Yoshida Akira Umino Harumi Kato Hiroyuki Tagawa Masao Nakagawa Noriko Fukuhara Sivasundaram Karnan Ichiro Takeuchi Toby D Hocking Kotaro Arita Kennosuke Karube Shinobu Tsuzuki Shigeo Nakamura Tomohiro Kinoshita Masao Seto |
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| Institution: | 1. Division of Molecular Medicine, Aichi Cancer Center Research Institute, , Nagoya, Japan;2. Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, , Nagoya, Japan;3. Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine, , Akita, Japan;4. Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, , Bethesda, Maryland, USA;5. Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, , Sendai, Japan;6. Department of Biochemistry, School of Medicine, Aichi Medical University, , Nagakute, Japan;7. Department of Computer Science/Scientific and Engineering Simulation, Nagoya Institute of Technology, , Nagoya, Japan;8. Department of Human Genetics, McGill University, , Montréal, Quebec, Canada;9. Department of Pathology and Clinical Laboratories, Nagoya University Hospital, , Nagoya, Japan |
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| Abstract: | Clonal heterogeneity in lymphoid malignancies has been recently reported in adult T‐cell lymphoma/leukemia, peripheral T‐cell lymphoma, not otherwise specified, and mantle cell lymphoma. Our analysis was extended to other types of lymphoma including marginal zone lymphoma, follicular lymphoma and diffuse large B‐cell lymphoma. To determine the presence of clonal heterogeneity, 332 cases were examined using array comparative genomic hybridization analysis. Results showed that incidence of clonal heterogeneity varied from 25% to 69% among different types of lymphoma. Survival analysis revealed that mantle cell lymphoma and diffuse large B‐cell lymphoma with clonal heterogeneity showed significantly poorer prognosis, and that clonal heterogeneity was confirmed as an independent predictor of poor prognosis for both types of lymphoma. Interestingly, 8q24.1 (MYC) gain, 9p21.3 (CDKN2A/2B) loss and 17p13 (TP53, ATP1B2, SAT2, SHBG) loss were recurrent genomic lesions among various types of lymphoma with clonal heterogeneity, suggesting at least in part that alterations of these genes may play a role in clonal heterogeneity. |
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| Keywords: | Array comparative genomic hybridization heterogeneity malignant lymphoma patient outcome assessment tumor cell population |
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