RT Journal Article
SR Electronic
T1 Prevalence and clinical outcomes of germline variants among patients with myeloid neoplasms
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP jcp-2023-209264
DO 10.1136/jcp-2023-209264
A1 Kongkiatkamon, Sunisa
A1 Niparuck, Pimjai
A1 Rattanathammethee, Thanawat
A1 Kobbuaklee, Sirorat
A1 Suksusut, Amornchai
A1 Wudhikarn, Kitsada
A1 Ittiwut, Chupong
A1 Chetruengchai, Wanna
A1 Chuncharunee, Suporn
A1 Bunworasate, Udomsak
A1 Suphapeetiporn, Kanya
A1 Rojnuckarin, Ponlapat
A1 Polprasert, Chantana
YR 2024
UL http://jcp.bmj.com/content/early/2024/05/21/jcp-2023-209264.abstract
AB Aims Myeloid neoplasms (MNs) with germline predisposition have been recognised as a distinct entity. Emerging evidence suggests that sporadic myelodysplastic syndromes may also harbour undetected germline predispositions. We investigated germline alterations in a cohort of 122 adult Thai MNs.Methods MN patients were recruited and tested for germline variants using deep targeted next-generation sequencing. The germline variant was filtered using American College of Medical Genetics classifications and then evaluated for the association with clinical characteristics and outcomes.Results Our findings revealed pathogenic/likely pathogenic germline alterations in 12 (10%) of the patients. These germline lesions were commonly found in the DNA damage response pathway (n=6, 50%). We also identified novel deleterious FANCAA1219GfsTer59 variants in two patients diagnosed with secondary acute myeloid leukaemia (sAML) from aplastic anaemia and AML with myelodysplasia related. Among sAML, individuals with germline mutations had inferior overall survival compared with those with wild-type alleles (2 months vs 12 months) with HR 4.7 (95% CI 1.0 to 20), p=0.037. Therefore, the presence of pathogenic or likely pathogenic mutations may be linked to inferior survival outcomes.Conclusions Our study highlighted that the prevalence of germline predisposition in Southeast Asian populations is comparable to that in Caucasians. This underscores the importance of germline genetic testing within the Asian population.Data are available on reasonable request.