COMy 2018 | Cytogenetics and genetics

The MM Hub were delighted to attend the 4th World Congress on Controversies in Multiple Myeloma (COMy) held in Paris, France, from 3-5 May 2018. The opening session of the congress focused on ‘Advances in disease biology’ and was moderated by Evangelos Terpos, from the Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece and Hervé Avet-Loiseau, from the Cancer Research Center of Toulouse, Toulouse, France.

Professor Hervé Avet-Loiseau gave the first talk of this session focusing on cytogenetics and genomics. He began by presenting a graph to compare the survival estimates for patients with low-, medium- and high- risk multiple myeloma (MM) (using FISH), and it was in this study that the t(4;14) abnormality was found to no longer fit with high-risk criteria, suggesting that the IMWG risk criteria needs revision. This study also suggested that MM patients with the translocation t(14;16) should not be classified as ‘high-risk’ and also that the role of ‘1q’ and ‘del(1p32)’ needed to be re-assessed.

Professor Avet-Loiseau then discussed the prognostic implications of mutations in myeloma, explaining that more data is required, as to date no prognostic impact has been observed with frequently mutated genes such as KRAS, NRAS, DIS3, BRAF, and FAM46C. So far, the only frequently mutated gene linked to prognosis is TP53, whereas mutations in other genes are very rare and have not yet shown any clear prognostic value.

The use of targeted exome sequencing (ES) in several panels was then described. Professor Avet-Loiseau’s group conducted a panel in which they identified 246 genes that are recurrently mutated in MM, in addition to 2,548 single nucleotide polymorphisms (SNPs) and whole IGH sequences related to 14q32 translocations. This panel was used to assess changes in copy number (such as 17p, 1p32, 1q gains and trisomies), all 14q32 translocations and mutations (especially TP53).

Professor Avet-Loiseau concluded by stating that new generation sequencing (NGS) should be used to unravel chromosomal abnormalities that have a prognostic impact in MM. He believes that targeted ES should be part of a routine risk assessment, and could possibly be used for targeted therapy. Additionally, he mentioned the use of whole genome sequencing (WGS) for research, the use of whole exome sequencing (WES) for subclonality and single cell analyses, and finally the use of RNASeq for transcriptomic heterogeneity and single-cell analyses.