A genome scan of 18 families with chronic lymphocytic leukaemia

Goldin, Lynn R.; Ishibe, Naoko; Sgambati, Maria; Marti, Gerald E.; Fontaine, Laura; Lee, Maxwell P.; Kelley, Jenny M.; Scherpbier, Titia; Buetow, Kenneth H.; Caporaso, Neil E.

doi:10.1046/j.1365-2141.2003.04372.x

Cited by 49 publications

(46 citation statements)

References 25 publications

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“…[32][33][34][35] In a genomewide scan of 18 CLL families, 36 we did not identify any significant linkage regions segregating in families, although a few regions had elevated linkage statistics, including regions on chromosomes 12, 13, 6, and 17 that overlap with cytogenetic abnormalities found in CLL. Linkage studies with larger sample sizes are clearly needed.…”

Section: Discussionmentioning

confidence: 99%

Familial risk of lymphoproliferative tumors in families of patients with chronic lymphocytic leukemia: results from the Swedish Family-Cancer Database

Goldin

Pfeiffer

et al. 2004

Blood

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Section: Discussionmentioning

confidence: 99%

Familial risk of lymphoproliferative tumors in families of patients with chronic lymphocytic leukemia: results from the Swedish Family-Cancer Database

Goldin

Pfeiffer

et al. 2004

Blood

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“…Two genome-wide linkage scans have been conducted to date. The first reported by Goldin et al 11 in 2003 used 359 microsatellite markers to genotype 18 CLL families. In 2005, a second genome-wide scan of 105 families segregating CLL with or without additional B-cell LPD cases was conducted using the Affymetrix Mapping 10Kv131 array, which contained approximately 11 500 single nucleotide polymorphisms (SNPs).…”

Section: B-cell Chronic Lymphocytic Leukemia (Cll [Mim No 151400])mentioning

confidence: 99%

A high-density SNP genome-wide linkage search of 206 families identifies susceptibility loci for chronic lymphocytic leukemia

Sellick

Goldin

Wild

et al. 2007

Blood

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Chronic lymphocytic leukemia (CLL) and other B-cell lymphoproliferative disorders display familial aggregation. To identify a susceptibility gene for CLL, we assembled families from the major European (ICLLC) and American (GEC) consortia to conduct a genome-wide linkage analysis of 101 new CLL pedigrees using a high-density single nucleotide polymorphism (SNP) array and combined the results with data from our previously reported analysis of 105 families. Here, we report on the combined analysis of the 206 families. Multipoint linkage analyses were undertaken using both nonparametric (model-free) and parametric (modelbased) methods. After the removal of high linkage disequilibrium SNPs, we obtained a maximum nonparametric linkage (NPL) score of 3.02 (P ‫؍‬ .001) on chromosome 2q21.2. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) score under a common recessive model of disease susceptibility (HLOD ‫؍‬ 3.11; P ‫؍‬ 7.7 ؋ 10 ؊5 ), which was significant at the genome-wide level. In addition, 2 other chromosomal positions, 6p22.1 (corresponding to the major histocompatibility locus) and 18q21.1, displayed HLOD scores higher than 2.1 (P < The striking multiple-case families reported in the literature provide substantive evidence for an inherited predisposition to CLL 2-4 and suggest the existence of susceptibility alleles with pleiotropic effects. 2,10 Case-control and cohort studies that have systematically estimated the familial risk of CLL and other LPDs have shown that most B-cell LPDs display site-specific elevated familial risks, 5-9 but particularly CLL, where risks are increased 3-to 7-fold in first-degree relatives of cases. Furthermore, such studies have demonstrated that familial associations exist between the different types of B-cell LPDs with risks of NHL and HL showing 2-fold increases in relatives of CLL cases..These observations provide a strong rationale for searching for predisposition genes for CLL through linkage searches of multiplecase families. Two genome-wide linkage scans have been conducted to date. The first reported by Goldin et al 11 in 2003 used 359 microsatellite markers to genotype 18 CLL families. In 2005, a second genome-wide scan of 105 families segregating CLL with or without additional B-cell LPD cases was conducted using the Affymetrix Mapping 10Kv131 array, which contained approximately 11 500 single nucleotide polymorphisms (SNPs). 12 In both studies, analyses provided evidence for susceptibility at a number of loci, but none achieved statistical significance, suggesting that a much larger familial sample was required to identify CLL predisposition loci.To address this, we have undertaken a further genome-wide linkage scan of an additional 101 families ascertained through the International CLL Consortium (ICLLC) and the Genetic Epidemiology of CLL (GEC) consortia. This search was conducted using high-density SNP arrays, thereby allowing us to pool findings with data generated from our previous scan of 105 families and in so An Inside Blood...

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“…This determines in part how frequent MBL is in the general population (11)(12)(13) and how it varies in key subgroups such as families (14,15)? While the reported age-adjusted population prevalence has been consistent, altered protocols predictably result in detection of lower (16) or higher (11) rates.…”

Section: Definitionmentioning

confidence: 99%

Monoclonal B cell lymphocytosis: Clinical and population perspectives

Caporaso

Marti

Landgren

et al. 2010

Cytometry Part B Clinical

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Monoclonal B Cell Lymphocytosis (MBL) refers to clones of CLL-like cells that exhibit CLL characteris-Five years after the formal description of monoclonal B cell lymphocytosis (MBL) as a uniform nomenclature for CLL-like cells clones that fall short of the numbers required for CLL diagnosis (1,2), the clinical, demographic and molecular features have begun to come into better focus. This report examines offers a clinical perspective on the controversies and suggests studies required for further progress. We discuss the definition, population features, clinical features, molecular components, and finally some recommendations for research directions. DEFINITIONThe original MBL definition (2) consolidated numerous earlier reports of B-cell clones (3,4) noted in diverse settings and distinguished an entity limited to monoclonal B-cell expansions with CLL-like characteristics that did not meet the absolute lymphocyte count (ALC) threshold for CLL. Some related and more rare subgroups (e.g., those with CD20 bright, CD5-cells) were included as distinct subgroups (1,2,5). However, there is an ongoing issue as to whether these should be separated to provide a more CLL-specific MBL definition (6).A recent revision of the definition of CLL has altered the ALC ceiling (7). The revised CLL definition requires an absolute B-lymphocyte count of greater than 5000 cells per cubic milliliter. This has important implications regarding the prevalence of MBL and CLL and the likelihood of a precursor state (MBL) progressing to CLL. Based on this classification change alone, numbers of CLL cases will decrease (because some individuals previously classified as having CLL will now be reclassified as MBL), MBL cases will increase, and the probability of progression to overt CLL will increase.

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A genome scan of 18 families with chronic lymphocytic leukaemia

Cited by 49 publications

References 25 publications

Familial risk of lymphoproliferative tumors in families of patients with chronic lymphocytic leukemia: results from the Swedish Family-Cancer Database

Familial risk of lymphoproliferative tumors in families of patients with chronic lymphocytic leukemia: results from the Swedish Family-Cancer Database

A high-density SNP genome-wide linkage search of 206 families identifies susceptibility loci for chronic lymphocytic leukemia

Monoclonal B cell lymphocytosis: Clinical and population perspectives

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