Mutational analysis of extranodal marginal zone lymphoma using next generation sequencing

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Extranodal marginal zone lymphoma, a type of low-grade B-cell lymphoma, is also known as MALT lymphoma.
• Next-generation sequencing (NGS) is a powerful technology for analyzing DNA, enabling simultaneous sequencing of numerous DNA strands.

Purpose of the Study:

• To investigate the genomic landscape of gastric and small intestine MALT lymphoma using NGS.
• To identify potential genetic variants, including single nucleotide variations (SNVs), insertions/deletions (InDels), and copy number variations (CNVs).

Main Methods:

• DNA extraction from paraffin-embedded MALT lymphoma tissue samples (gastric n=1, small intestine n=4).
• Next-generation sequencing (NGS) performed using HemaSCAN™, a custom panel targeting 426 genes crucial for blood cancers.
• Analysis of genomic variants including SNVs, InDels, and CNVs, categorizing them as annotated, known, or novel.

Main Results:

• NGS identified various genomic variants in MALT lymphoma samples.
• An annotated variant, erb-b2 receptor tyrosine kinase 2 gene amplification, was found in one patient.
• Known and novel variants (SNVs, InDels, CNVs) in genes such as SETBP6, Runt-related transcription factor 1, Ki-67, zinc finger protein 703, and NOTCH1 were observed in multiple patients.
• Frameshift InDels were identified in B-cell lymphoma/leukemia 10, DEAD-box helicase 3 X-linked, forkhead box O3, and mucin 2 genes in one patient.

Conclusions:

• This study provides initial insights into the genetic alterations in MALT lymphoma using NGS.
• The identified mutations require further investigation to ascertain their 'actionable' potential for targeted MALT lymphoma therapies.
• Additional research is necessary to establish the correlation between specific genetic mutations and the pathogenesis of MALT lymphoma.