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Although the overall incidence of MGUS progression is 1 per year, it is now possible to more accurately predict the risk of progression based on a new risk\u2010stratification model. However, it is still hard to design chemopreventive trials given that the absolute risk of progression per year is low, even in the high\u2010risk group. Therefore, further improvements in estimating the risk of progression are needed. Roughly 50% of MGUS may originate from primary translocation events at the heavy\u2010chain immunoglobulin locus at chromosome 14q32. In most of the remaining MGUS patients, the initiating event is associated with genomic instability that results in hyperdiploidy of certain odd numbered chromosomes. Cytogenetically distinct subtypes of MGUS may carry significant differences in the risk of progression to malignancy. New markers, such as measures of bone marrow angiogenesis and circulating plasma cells may be additional prognostic factors. A better understanding of the mechanisms underlying the transition of normal plasma cells to the MGUS phenotype, and the transition of MGUS to myeloma or related malignancy, will help identify new risk factors for progression and new targets for chemopreventive interventions.<\/jats:p>","DOI":"10.1111\/j.1365-2141.2006.06235.x","type":"journal-article","created":{"date-parts":[[2006,8,7]],"date-time":"2006-08-07T15:06:38Z","timestamp":1154963198000},"page":"573-589","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":180,"title":["Monoclonal gammopathy of undetermined significance"],"prefix":"10.1111","volume":"134","author":[{"given":"Robert A.","family":"Kyle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Vincent Rajkumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,8,18]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1001\/archinte.1975.00330010064009","article-title":"Monoclonal gammopathy in lymphoma","volume":"135","author":"Alexanian R.","year":"1975","journal-title":"Archives of Internal Medicine"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20184"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-129-4-199808150-00005"},{"key":"e_1_2_12_5_1","first-page":"572","article-title":"Artifactual hypercalcemia in multiple myeloma","volume":"57","author":"Annesley T.M.","year":"1982","journal-title":"Mayo Clinic Proceedings"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.162.4.464"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.20157"},{"key":"e_1_2_12_8_1","first-page":"5640","article-title":"High incidence of translocations t(11;14)(q13;q32) and t(4;14)(p16;q32) in patients with plasma cell malignancies","volume":"58","author":"Avet\u2010Loiseau H.","year":"1998","journal-title":"Cancer Research"},{"key":"e_1_2_12_9_1","first-page":"4546","article-title":"14q32 translocations and monosomy 13 observed in monoclonal gammopathy of undetermined significance delineate a multistep process for the oncogenesis of multiple myeloma. 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