Browsing by Author "Goldin, Lynn R"
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Item Open Access Association of elevated serumfree light chains with chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis.(Blood cancer journal, 2019-08-05) Clay-Gilmour, Alyssa I; Rishi, Abdul R; Goldin, Lynn R; Greenberg-Worisek, Alexandra J; Achenbach, Sara J; Rabe, Kari G; Maurer, Matthew J; Kay, Neil E; Shanafelt, Tait D; Call, Timothy G; Brice Weinberg, J; Camp, Nicola J; Cerhan, James R; Leis, Jose; Norman, Aaron; Murray, David L; Vincent Rajkumar, S; Caporaso, Neil E; Landgren, Ola; McMaster, Mary L; Slager, Susan L; Vachon, Celine MChronic lymphocytic leukemia (CLL) and its precursor, monoclonal B-cell lymphocytosis (MBL), are heritable. Serumfree light-chain (sFLC) measures are a prognostic factor for CLL, but their role in susceptibility to CLL is not clear. We investigated differences between sFLC measurements in pre-treatment serum from five groups to inform the association of sFLC with familial and sporadic CLL: (1) familial CLL (n = 154), (2) sporadic CLL (n = 302), (3) familial MBL (n = 87), (4) unaffected first-degree relatives from CLL/MBL families (n = 263), and (5) reference population (n = 15,396). The percent of individuals having elevated monoclonal and polyclonal sFLCs was compared using age-stratified and age- and sex-adjusted logistic regression models. In age groups >50 years, monoclonal sFLC elevations were increased in sporadic and familial CLL cases compared to the reference population (p's < 0.05). However, there were no statistically significant differences in sFLC monoclonal or polyclonal elevations between familial and sporadic CLL cases (p's > 0.05). Unaffected relatives and MBL cases from CLL/MBL families, ages >60 years, showed elevated monoclonal sFLC, compared to the reference population (p's < 0.05). This is the first study to demonstrate monoclonal sFLC elevations in CLL cases compared to controls. Monoclonal sFLC levels may provide additional risk information in relatives of CLL probands.Item Open Access Detectable clonal mosaicism from birth to old age and its relationship to cancer.(Nature genetics, 2012-05-06) Laurie, Cathy C; Laurie, Cecelia A; Rice, Kenneth; Doheny, Kimberly F; Zelnick, Leila R; McHugh, Caitlin P; Ling, Hua; Hetrick, Kurt N; Pugh, Elizabeth W; Amos, Chris; Wei, Qingyi; Wang, Li-e; Lee, Jeffrey E; Barnes, Kathleen C; Hansel, Nadia N; Mathias, Rasika; Daley, Denise; Beaty, Terri H; Scott, Alan F; Ruczinski, Ingo; Scharpf, Rob B; Bierut, Laura J; Hartz, Sarah M; Landi, Maria Teresa; Freedman, Neal D; Goldin, Lynn R; Ginsburg, David; Li, Jun; Desch, Karl C; Strom, Sara S; Blot, William J; Signorello, Lisa B; Ingles, Sue A; Chanock, Stephen J; Berndt, Sonja I; Le Marchand, Loic; Henderson, Brian E; Monroe, Kristine R; Heit, John A; de Andrade, Mariza; Armasu, Sebastian M; Regnier, Cynthia; Lowe, William L; Hayes, M Geoffrey; Marazita, Mary L; Feingold, Eleanor; Murray, Jeffrey C; Melbye, Mads; Feenstra, Bjarke; Kang, Jae H; Wiggs, Janey L; Jarvik, Gail P; McDavid, Andrew N; Seshan, Venkatraman E; Mirel, Daniel B; Crenshaw, Andrew; Sharopova, Nataliya; Wise, Anastasia; Shen, Jess; Crosslin, David R; Levine, David M; Zheng, Xiuwen; Udren, Jenna I; Bennett, Siiri; Nelson, Sarah C; Gogarten, Stephanie M; Conomos, Matthew P; Heagerty, Patrick; Manolio, Teri; Pasquale, Louis R; Haiman, Christopher A; Caporaso, Neil; Weir, Bruce SWe detected clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells with the same abnormal karyotype (>5-10%; presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rapidly rises to 2-3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions with genes previously associated with these cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer before DNA sampling, those without a previous diagnosis have an estimated tenfold higher risk of a subsequent hematological cancer (95% confidence interval = 6-18).