HAEM5:Myelodysplastic neoplasm with biallelic TP53 inactivation: Difference between revisions

==Gene Mutations (SNV/INDEL)==

At least one mutation involving ''[[TP53]]'' is required to establish a diagnosis of MDS bi''TP53''; a second distinct mutation involving ''TP53'', fulfilling diagnostic criteria without deletion or copy neutral LOH, is identified in approximately one third of patients with MDS-bi''TP53''.<ref name=":2" /><ref name=":0" /> ''TP53'' mutations reported in MDS-bi''TP53'' show a similar pattern of distribution to those previously reported, primarily clustering in the DNA-binding domain with smaller numbers of (primarily truncating) mutations upstream (extending to the transactivation domain) or downstream (extending downstream of the oligomerization domain); available data suggest approximately 70% of mutations to be missense variants, 28% (a higher frequency than was observed in MDS with monoallelic ''TP53'' mutation) to be truncating (including nonsense, frameshift, splice site, and nonstop variants), and a small fraction to be in-frame deletions or insertions.<ref name=":0" /> In MDS-bi''TP53'', 20% of ''TP53'' variants identified were accounted for by hotspot mutations affecting amino acids 273, 220, 248, and 175 (in order of descending frequency). Variants identified in the context of multiple distinct ''TP53'' mutations have been reported with a median VAF of 32% (range: 2% to 52%) while those associated with a second hit resulting from ''TP53'' locus deletion or copy-neutral LOH have a reported median VAF of 41% (2% to 92% with a bimodal distribution) and 71% (2% to 98%), respectively.<ref name=":0" />