Assessing copy number aberrations and copy-neutral loss-of-heterozygosity across the genome as best practice: An evidence-based review from the Cancer Genomics Consortium (CGC) working group for chronic lymphocytic leukemia

Chun, Kathy; Wenger, Gail D.; Chaubey, Alka; Dash, Durga Prasad; Kanagal‐Shamanna, Rashmi; Kantarci, Sibel; Kolhe, Ravindra; Dyke, Daniel L. Van; Wang, Lu; Wolff, Daynna J.; Miron, Patricia M.

doi:10.1016/j.cancergen.2018.07.004

Cited by 27 publications

(27 citation statements)

References 133 publications

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“…In our hands, the whole analytic procedure for one LYNX run (12 samples) takes around four weeks, including the laboratory part (5 days), the bioinformatic analysis (4 days), data interpretation and reporting (2 weeks). We would like to emphasize major benefits of the assay: i) the analysis of cnLOHs that occur in B-cell neoplasms frequently 71,72 and are indistinguishable by the standard FISH method, ii) the complete picture of IG/TR clonotypes, iii) the J o u r n a l P r e -p r o o f exact breakpoint localization of both rearrangements and translocations allowing allele-specific assay design crucial for MRD monitoring, and iv) short turnaround time and lower personnel demands in comparison with the utilization of parallel methods to gather information about all biomarkers.…”

Section: Discussionmentioning

confidence: 99%

LYmphoid NeXt-Generation Sequencing (LYNX) Panel

Navrkalová

Plevová

Hynšt

et al. 2021

The Journal of Molecular Diagnostics

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Section: Discussionmentioning

confidence: 99%

LYmphoid NeXt-Generation Sequencing (LYNX) Panel

Navrkalová

Plevová

Hynšt

et al. 2021

The Journal of Molecular Diagnostics

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“…[13][14][15] Even though CBA has been the gold standard method to identify CK, in the last decade genomic microarrays (GM) have emerged as a valuable tool for genome-wide screening in CLL. [16][17][18][19][20] Indeed, some studies have correlated the genomic complexity detected by GM to progressive disease and poorer response rates to treatment. [21][22][23] Nonetheless, although some European countries have replaced conventional techniques by GM, standard criteria to analyze and define genomic complexity by GM are still needed.…”

Section: Introductionmentioning

confidence: 99%

Chromosome banding analysis and genomic microarrays are both useful but not equivalent methods for genomic complexity risk stratification in chronic lymphocytic leukemia patients

et al. 2021

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Genome complexity has been associated with poor outcome in patients with chronic lymphocytic leukemia (CLL). Previous cooperative studies established five abnormalities as the cut-off that best predicts an adverse evolution by chromosome banding analysis (CBA) and genomic microarrays (GM). However, data comparing risk stratification by both methods are scarce. Herein, we assessed a cohort of 340 untreated CLL patients highly enriched in cases with complex karyotype (CK, 46.5%) with parallel CBA and GM studies. Abnormalities found by both techniques were compared. Prognostic stratification in three risk groups based on genomic complexity [0-2, 3-4 and ≥5 abnormalities] was also analyzed. No significant differences in the percentage of patients classified into each category were detected, but only a moderate agreement was observed between methods when focusing in individual cases (κ=0.507; p

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“…In addition, by CBA unbalanced translocations and complex derivative chromosomes can also be found. Accordingly, genomic microarrays demonstrated to be a valuable technique to screen for genome-wide unbalanced alterations, showing that more than 90% of CLL analyzed harbor gains or losses [12][13][14][15][16] and that the number of alterations detected by microarray correlates with poor prognosis and poor response to treatment. [17][18][19] In contrast to other B-cell malignancies, CLL has a low frequency of recurrent translocations and this makes their identification and reporting crucial for the recognition of the recurrent ones, increasing the likelihood of identifying genes possibly involved in the pathogenesis of the neoplasia.…”

Section: Discussionmentioning

confidence: 99%

Balanced and unbalanced translocations in a multicentric series of 2843 patients with chronic lymphocytic leukemia

Costa

Granada

Espinet

et al. 2021

Genes Chromosomes & Cancer

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Chromosomal translocations in chronic lymphocytic leukemia (CLL) are very rare, and therefore systematic analysis of large series of cases is needed to allow the identification of recurrent rearrangements, breakpoints involved, and target genes.The aims of the present study were to identify new translocations and their clinical impact and to establish their frequency in a large cohort of 2843 CLL patients. By conventional cytogenetics 250 translocations were identified in 215 (7.5%) patients, 186 (74%) were apparently balanced and 64 (26%) were unbalanced. All chromosomes were involved in translocations, except Y chromosome. The chromosomes more frequently translocated were in decreasing frequency chromosomes 14, 18, 13, 17, 1, 6, 2, 3, 8, and 11. Translocations were found in the karyotypes either as the unique chromosomal abnormality (27%), associated with another alteration (24%), or as a part of a complex karyotype (CK, 48%). A large proportion of rearranged breakpoints involved genes related to CLL such as IGH (14q32), RB1, MIR15A, MIR16-1 (13q14), BCL2 (18q21), IGL (22q11.2), TP53 (17p13), IRF4 (6p25-p23), ATM (11q22), and CDK6 (7q21). Overall, 76 novel CLL translocations were identified, including a recurrent t(8;11) (p21;q21-23). Whole-genome sequencing and/or copy-number microarray data of 24 cases with translocations confirmed all rearrangements, enabled refinement of 3 karyotypes and all breakpoints at gene level. The projected survival and time to first treatment significantly decreased linearly with the number of translocations. In summary, this study allowed to establish the frequency of translocations (7.5%) and to identify new translocations in a cohort of 2843 CLL patients.

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Assessing copy number aberrations and copy-neutral loss-of-heterozygosity across the genome as best practice: An evidence-based review from the Cancer Genomics Consortium (CGC) working group for chronic lymphocytic leukemia

Cited by 27 publications

References 133 publications

LYmphoid NeXt-Generation Sequencing (LYNX) Panel

LYmphoid NeXt-Generation Sequencing (LYNX) Panel

Chromosome banding analysis and genomic microarrays are both useful but not equivalent methods for genomic complexity risk stratification in chronic lymphocytic leukemia patients

Balanced and unbalanced translocations in a multicentric series of 2843 patients with chronic lymphocytic leukemia

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