Background: Therapy-related Myelodysplastic Syndrome/Acute Myeloid Leukemia (t-MDS/AML) is a serious complication for cancer patients undergoing chemotherapy or radiation treatment. Determining the mechanisms behind disease progression will help to design targeted treatment strategies. The objective of this study was to investigate the genetic basis for t-MDS/AML development.

Case: Exome sequencing analysis was performed for a t-MDS/AML patient to investigate the somatic mutation in coding genes at diagnosis, remission, allo-transplantation, and relapse.

Results: The study observed dynamic changes of somatic mutation during disease development. A TGTG insertion mutation was indentified at exon 3 in Tet methylcytosine dioxygenase 2 (TET2) at diagnosis. This mutation caused a frameshift, generating a pre-matured stop codon downstream, and leading to loss-of-function of TET2. At post-allotransplantation and relapse, this mutation decreased to basal levels.

Conclusions: The results suggest that the TET2-mutated clone might play more important roles in initiation than in relapse of t-MDS/AML, in which a new clone(s) with wild-type TET2 may became dominant.