Sang-Yong Shin1, Hyeon-Seok Eom2, Ji Yeon Sohn1, Hyewon Lee3, Boram Park4, Jungnam Joo4, Ja-Hyun Jang5, Mi-Na Lee6, Jung Kwon Kim1, Sun-Young Kong7. 1. Department of Laboratory Medicine, Center for Diagnostic Oncology and Translational Epidemiology Research Branch, Hospital and Research Institute, National Cancer Center, Goyang, Korea. 2. Department of Hematology-Oncology, Center for Hematologic Malignancy, National Cancer Center, Goyang, Korea; Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea. 3. Department of Hematology-Oncology, Center for Hematologic Malignancy, National Cancer Center, Goyang, Korea; Hematologic Malignancy Branch, Research Institute, National Cancer Center, Goyang, Korea. 4. Biometric Research Branch, Research Institute, National Cancer Center, Goyang, Korea. 5. Green Cross Genome, Yongin, Korea. 6. Green Cross Laboratories, Yongin, Korea. 7. Department of Laboratory Medicine, Center for Diagnostic Oncology and Translational Epidemiology Research Branch, Hospital and Research Institute, National Cancer Center, Goyang, Korea; Department of Hematology-Oncology, Center for Hematologic Malignancy, National Cancer Center, Goyang, Korea; Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea; Translational Epidemiology Research Branch, Research Institute, National Cancer Center, Goyang, Korea. Electronic address: ksy@ncc.re.kr.
Abstract
BACKGROUND: Cytogenetic analysis aides in risk stratification for patients with multiple myeloma (MM). Although several cytogenetic aberrations have been reported to be prognostic, less is known about the association between the presence of monosomies and prognosis. The present study evaluated the prevalence and prognostic implications of monosomies in patients with MM. MATERIALS AND METHODS: Karyotypes were determined using conventional cytogenetics and fluorescence in situ hybridization (FISH). The prognostic effect of monosomies was evaluated by comparison with the clinical factors in MM patients with normal karyotypes. RESULTS: Karyotypes were successfully determined in 167 of the 170 patients with MM. Of these 167 patients, 52 (31.1%) had abnormal karyotypes. Univariable analyses showed that a normal karyotype, hypodiploidy, monosomies of chromosomes 13 and 16, deletion or monosomy of 13q14, and loss of X detected by metaphase analysis were each associated with reduced progression-free survival (P < .05 for each). Univariable analyses showed that a normal karyotype, hypodiploidy, monosomies of chromosomes 13 and 16, deletion or monosomy of 13q14 detected by metaphase analysis and FISH-determined RB1 (13q)/TP53 (17p) deletion were each associated with reduced overall survival (P < .05 for each). Multivariable analysis showed that hypodiploidy detected by metaphase analysis was independently prognostic of shorter progression-free survival (P < .05 for each) and that hypodiploidy, monosomy 16, and loss of Y chromosome and FISH-determined TP53 (17p) deletion were associated with reduced overall survival (P < .05 for each). CONCLUSION: In addition to known cytogenetic abnormalities, such as monosomy 13, hypodiploidy, and TP53 (17p) deletion, monosomy 16 and loss of the Y chromosome have adverse prognostic implications in patients with MM.
BACKGROUND: Cytogenetic analysis aides in risk stratification for patients with multiple myeloma (MM). Although several cytogenetic aberrations have been reported to be prognostic, less is known about the association between the presence of monosomies and prognosis. The present study evaluated the prevalence and prognostic implications of monosomies in patients with MM. MATERIALS AND METHODS: Karyotypes were determined using conventional cytogenetics and fluorescence in situ hybridization (FISH). The prognostic effect of monosomies was evaluated by comparison with the clinical factors in MM patients with normal karyotypes. RESULTS: Karyotypes were successfully determined in 167 of the 170 patients with MM. Of these 167 patients, 52 (31.1%) had abnormal karyotypes. Univariable analyses showed that a normal karyotype, hypodiploidy, monosomies of chromosomes 13 and 16, deletion or monosomy of 13q14, and loss of X detected by metaphase analysis were each associated with reduced progression-free survival (P < .05 for each). Univariable analyses showed that a normal karyotype, hypodiploidy, monosomies of chromosomes 13 and 16, deletion or monosomy of 13q14 detected by metaphase analysis and FISH-determined RB1 (13q)/TP53 (17p) deletion were each associated with reduced overall survival (P < .05 for each). Multivariable analysis showed that hypodiploidy detected by metaphase analysis was independently prognostic of shorter progression-free survival (P < .05 for each) and that hypodiploidy, monosomy 16, and loss of Y chromosome and FISH-determined TP53 (17p) deletion were associated with reduced overall survival (P < .05 for each). CONCLUSION: In addition to known cytogenetic abnormalities, such as monosomy 13, hypodiploidy, and TP53 (17p) deletion, monosomy 16 and loss of the Y chromosome have adverse prognostic implications in patients with MM.
Authors: Franziska Büscheck; Christoph Fraune; Seyedehmina Garmestani; Ronald Simon; Martina Kluth; Claudia Hube-Magg; Kathrin Ketterer; Christian Eichelberg; Doris Höflmayer; Frank Jacobsen; Corinna Wittmer; Waldemar Wilczak; Guido Sauter; Margit Fisch; Till Eichenauer; Michael Rink Journal: Ann Transl Med Date: 2021-02