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Updated: Sep 25, 2026
Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
A genome scan of 18 families with chronic lymphocytic leukaemia
Lynn R Goldin1, Naoko Ishibe, Maria Sgambati
1Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute/NIH, 6120 Executive Boulevard, Room 7008, MSC 7236, Bethesda, MD 20892-7236, USA. goldinl@mail.nih.gov
Insights
This study investigated genetic factors contributing to chronic lymphocytic leukemia (CLL) by analyzing DNA from 18 families. While no specific susceptibility genes were confirmed, several chromosomal regions showed potential links, warranting further research into CLL genetics.
Area of Science:
- Genetics
- Oncology
- Leukemia Research
Background:
- Chronic lymphocytic leukemia (CLL) is a common leukemia in older adults, accounting for 30% of all leukemia cases.
- Familial aggregation of CLL suggests a genetic component, but the inheritance pattern and specific genes remain unknown.
- Cytogenetic abnormalities are common in CLL cells, but germline susceptibility genes have not been identified.
Purpose of the Study:
- To identify potential genetic susceptibility loci for chronic lymphocytic leukemia (CLL) within families.
- To investigate the mode of inheritance for familial CLL.
- To correlate potential germline changes with known cytogenetic abnormalities in CLL.
Main Methods:
- Collected clinical data and DNA samples from 18 families with at least two CLL patients.
- Performed a genome-wide scan using 359 markers from the ABI 28-panel linkage mapping set.
- Calculated multipoint LOD scores and non-parametric linkage scores, considering dominant/recessive inheritance and age-related penetrance.
Main Results:
- Identified regions on chromosomes 1, 3, 6, 12, 13, and 17 with LOD scores of 1.0 or greater.
- No specific loci reached statistical significance for linkage.
- Four regions (6q, 13q, 12, and 17p) with positive LOD scores overlap with known cytogenetic abnormality sites in CLL.
Conclusions:
- The study identified candidate chromosomal regions for CLL susceptibility genes.
- These regions, particularly 6q, 13q, 12, and 17p, are promising for further investigation due to overlap with known CLL cytogenetic alterations.
- Further research is needed to confirm specific germline mutations responsible for familial CLL.
Abstract:
Chronic lymphocytic leukaemia (CLL) accounts for about 30% of all leukaemias and is most prevalent in older individuals. Significant familial aggregation has been demonstrated but the mode of inheritance is unknown. Recurrent cytogenetic abnormalities are frequently found in CLL tumour cells but no susceptibility genes have been confirmed. We have collected clinical data and biospecimens on families ascertained for having at least two living patients with CLL. The current study included DNA samples from 94 individuals (38 affected patients) in 18 families. We have carried out a genome scan using the ABI 28-panel medium density linkage mapping set (average spacing of 10 cM and average heterozygosity of 80%). Genotypes for 359 markers were scored. Multipoint limit of detection (lod) scores were calculated, assuming both dominant and recessive inheritance and allowing for increased penetrance with age and genetic heterogeneity. Non-parametric linkage scores were also calculated. Lod scores of 1.0 or greater were found on regions of chromosomes 1, 3, 6, 12, 13 and 17, but none of these loci achieved statistical significance. Four of these six regions (6q, 13q, 12 and 17p) coincide with areas where cytogenetic abnormalities are frequently observed in CLL tumour cells and are, therefore, strong candidate regions for containing germ line changes.
