Table 3.

Summary of Genetic, Epigenetic, and miRNA Studies.

Authors	Methodology	Source	Findings
Yamaguchi et al. Cancer, 1995.	IHC and reverse transcription (RT) PCR	Ten Japanese patients with nasal NK/T-cell lymphoma	Nine of the 10 patients were P-glycoprotein positive by IHC. MDR1 mRNA was detected in all seven pts examined by RT-PCR.
Wong et al. BJH, 1997.	Conventional karyotype	7 CD56+ leukemia/lym-phoma (2 extranasal, 1 nasal, 3 ANKL, 1 blastoid leukemia/lymphoma)	Del(6)(q21q25) is a recurring abnormality.
Siu et al. Am J Pathol, 1999.	CGH	Primary tumors from four nasal NK cell lymphomas, one nasal-type NK cell lym-phoma, and five NK cell lymphomas/leukemias	Deletions at 6q16-q27 (four cases), 13q14-q34 (three cases), 11q22-q25 (two cases), and 17p13 (two cases).
Ko et al. Cytometry, 2001.	CGH	7 nasal ENKTL (6 NK-ENKTL, 1 T-ENKTL)	Frequent DNA losses at 1p, 17p, and 12q and gains at 2q, 13q, and 10q. Infrequent loss of 6q comprise several candidate tumor suppressor genes (PRDM1, HACE1, FOX03, AIM1, ATG5).
Nakashima et al. Genes Chromosomes Cancer, 2005.	Homemade array-based CGH	10 aggressive NK-cell leukemia cases and 17 ENKTL, nasal type	Gain of 1q23.1–24.2 and 1q31.3–q44), and loss of 7p15.1–p22.3 and 17p13.1 occurred significantly more frequently in ENKTL. Gain of 2q, and loss of 6q16.1–q27, 11q22.3–q23.3, 5p14.1–p14.3, 5q34–q35.3, 1p36.23–p36.33, 2p16.1–p16.3, 4q12, and 4q31.3–q32.1 were nonsignificantly more common in ENKTL.
Iqbal et al. Leukemia, 2009.	CGH & GEP	NK cell lines & 7 patients with NK-cell malignancies	PRDM1 was the most likely tumor promoting gene in del6q21. ATG5 and AIM1 may also participate in the tumor development and progression.
Huang et al. Blood, 2010.	GEP	9 tumors (1 T-cell ENKTL, 8 NK-cell ENKTL) & 2 cell lines (SNK6 and SNK8)	Compared to normal NK cells, tumors were closer to activated than resting cells and overexpressed several genes related to vascular biology, EBV induced genes, and PDGFRA. Integrative analysis also evidenced deregulation of the tumor suppressor HACE1 in the frequently deleted 6q21 region.
Jiang et al. Nature Genetics, 2015.	Whole exome sequencing	25 de novo ENKTL	Recurrent mutations were most frequently located in the RNA helicase gene DDX3X (20%), tumor suppressors (TP53 & MGA), JAK-STAT pathway molecules (STAT3 & STAT5B), and epigenetic modifiers (MLL2, ARID1A, EP300, & ASXL3).
Kucuk et al. Clin Cancer Res, 2015.	Global promotor methylation analysis	12 ENKTL and 7 NK cell lines (NK92, KHYG1, YT, SNK1, SNK6, NKYS, & KAI3)	Identified 95 genes with strong evidence for being silenced because of promotor methylation, including BCL2L11 (BIM), DAPK1, PTPN6 (SHP1), TET2, SOCS6, and ASNS.