Eurofins Biomnis code

LLC

Specialty

Genetics

Clinical significance

The «LLC» NGS panel consists of an analysis of 28 genes: ARID1A/ATM/BAX/BCL2/BCOR/BIRC3/BRAF/BTK/CARD11/EGR2/EP300/FBXW7/HRAS/KRAS/MAP2K1/MCL1/MGA/MYD88/NFKBIE/NOTCH1/NRAS/PLCG2/POT1/RPS15/SAMHD1/SF3B1/TP53/XPO1. It has a triple diagnostic, prognostic and theranostic value and must be combined with a blood cytogenetic study and an analysis for IG-HV mutations. From a theranostic point of view, the CLL panel includes all the genes from the «LLC» panel presented above. From a prognostic point of view, the presence of a TP53 abnormality (del(17p) deletion or TP53 mutation) is the predominant prognostic value in CLL, followed by IGHV status. Both mutations status are included in the CLL-IPI score. However, other mutations (NOTCH1, SF3B1, ATM, BIRC3, XPO1, POT1, EGR2, RPS15, NFKBIE or MGA) are also associated with a poor prognosis. The exhaustive molecular result obtained with this panel provides the clinician with an additional help for the prognostic evaluation of CLL, particularly in the context of Rai 0. The CLL-IPS-Early-Stage score already takes into account the mutation status of the TP53, IGHV, ATM, MYD88, NOTCH1 and SF3B1 genes. It should be noted that the presence of a MYD88 mutation has no negative prognostic value in CLL. Associations between "cytogenetic abnormalities "and "molecular abnormalities" have also been reported: del(11q) deletion and ATM, BIRC3, SF3B1 or XPO1 mutations, trisomy 12 and NOTCH1, BIRC3 or FBXW7 mutations, del(13q) deletion and MYD88 or POT1 mutation. The association of these mutations could also have a more pronounced unfavourable prognostic value. Mutational co-occurrences have been reported (e.g. TP53-NOTCH1-XPO1). All the genes in the NGS "CLL" panel belong to different signalling pathways involved in CLL and thus contribute to a diagnostic help. The most frequently mutated genes are NOTCH1 (10~15%), SF3B1 (~10%), TP53 (5~8%), ATM (~5%), BIRC3, EGR2, FBXW7, MYD88, NFKBIE, POT1 and XPO1 (3~5%).

Preanalytics

• 5 ml EDTA whole blood or 2 ml EDTA bone marrow or DNA extracted : (200ng of DNA minimum)
•   Ambient temperature

• A tube specifically for this analysis : No

Further information

Samples to be collected from Monday to Friday
Sample must be refrigerated if transport is > 48 hours
Use the specific request form B8-INTGB: Malignant blood disorders
Attach:
- the results of the FBC- platelets
- the bone marrow report
- the immunophenotyping report
- Results of lymph node histology (if performed)

Specific equipment available

• S9L: Envelopes yellow for karyotypes LYON

Documents to download

• Specific request form B8-INTGB
• Information aimed at healthcare professionals(DP-INTGB)
• Panel form(DS119-INTGB)

Methodology

Method: Targeted sequencing of genes (NGS). - Library: Library Preparation Enzymatic Fragmentation Kit 2.0 Twist - NGS Platform: NovaSeq Illumina (2x150pb) - paired-end sequencing - Analysis software: Demultiplexage BCLconvert V3.10.5 / VarSome Pipeline version 11.8 (CE-IVD)

Turnaround time

10 days