Abstract 5225: CDK11B, PTPRN2 and WDPCP were frequently duplicated genes in refractory/relapsed normal karyotype AML patients: Identifying structural variations using whole genome sequencing
Authors: Youk Jeonghwan , Cho Sunghoon , Kim Daeyoon , Koh Youngil , Kim Inho , Choi Murim , Yoon Sung-Soo 
Published: July 2016

Abstract
Background
According to the NCCN guideline, the prognosis of acute myeloid leukemia with normal karyotype (NK-AML) is classified based on the mutational status of NPM1, FLT3-ITD or CEBPA. However, patients with NK-AML without the above mutations, who are in intermediate risk, still show various clinical outcomes. Unfortunately, refractory/relapsed patients with intermediate risk NK-AML cannot be predicted before cytotoxic chemotherapy, yet. With the advent of next generation sequencing technology, we tried to reveal prognostic molecular marker in intermediate risk NK-AML, especially focusing on large structural variations (SVs).
Methods
A total of nine patients with intermediate risk NK-AML patients were included. Whole genome sequencing (WGS) was performed using a pair of tumor and germline DNA of the patients. Leukemic blasts were obtained from bone marrow aspiration specimens of each patient at the time of diagnosis. As a germline control, epithelial cells were collected from saliva of each patient at the time of complete remission. Then, genomic DNA was massively sequenced using HiSeq X10 system (Illumina Inc., San Diego, CA, USA). Possible SVs including inversion, duplication and translocation were identified with BreakDancer (Washington University School of Medicine, St. Louis, MO, USA), Pindel (The Wellcome Trust Sanger Institute, Cambridge, UK) and Delly (European Molecular Biology Laboratory, Heidelberg, Germany). Possible SVs were considered when they were recurrently identified from the three pipelines.
Results
This cohort consisted of 7 males and 2 females (median age = 55.6 years old). None of them had secondary AML. Eight patients were relapsed after complete remission and the other patient was refractory to 1st line induction chemotherapy. Through WGS, 25 inversions, 67 duplications and 10 translocations were identified in nine patients. Among them, 4 inversions, 13 duplications and 2 translocations were recurrently mutated. Especially, CDK11B, PTPRN2 and WDPCP were frequently duplicated more than 40% of the patients.
Conclusions
In this study, we performed WGS to investigate SVs of refractory/relapsed NK-AML patients with intermediate risk. Among various mutations, duplications of CDK11B, PTPRN2 and WDPCP were highly prevalent, so they could be a possible prognostic biomarker in NK-AML with intermediate risk. Further functional validation is required in order to clarify their roles.
Citation Format: Jeonghwan Youk, Sunghoon Cho, Daeyoon Kim, Youngil Koh, Inho Kim, Murim Choi, Sung-Soo Yoon. CDK11B, PTPRN2 and WDPCP were frequently duplicated genes in refractory/relapsed normal karyotype AML patients: Identifying structural variations using whole genome sequencing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5225.