Duplex sequencing uncovers recurrent low-frequency cancer-associated mutations in KMT2A-rearranged infant acute leukemia

All patients had an underlying rearrangement of the KMT2A gene, either KMT2A::MLLT3 (n=5), KMT2A::AFF1 (n=12), KMT2A::MLLT1 (n=8) or KMT2A::MLLT10 (n=2). The median age of the cohort was 7 months.

Diagnostic sample from peripheral blod (n=11) or bone marrow (n=16) underwent the duplex sequencing library preparation as described in doi.org/10.1073/pnas.1208715109 and sequenced on the NextSeq 500 (Illumina, San Diego, CA, USA). A subset of variants were validated by targeted multiplex-PCR followed by NGS. In six patients with available relapse samples, a screening of diagnostic variants was performed by multiplex-PCR and NGS.