Regulation of deoxynucleotide metabolism in cancer: novel mechanisms and therapeutic implications

Table 1 Summary of the identified SAMHD1 alterations in various human cancers

Cancers	Identified SAMHD1 alterations				References
	Gene mutations		Epigenetic alterations	Consequences
	Frequencies	Amino acid changes (domain locations)^a, ^b	Epigenetic alterations	Consequences
Breast cancer	0.4 %^c (4/981 cases)	N.A.	N.A.	Reduced SAMHD1 protein	[11, 17]
Chronic lymphocytic leukemia	2.5 %^a [13] (4/160 cases)	N.A.	N.A.	Reduced SAMHD1 mRNA and protein	[11, 13, 16]
Colorectal cancer	2.2 %^c (5/223 cases)	F59C (SAM domain)^d D207Y (HD domain)^d R226H (HD domain)^d T232M (HD domain)^d S247Y (HD domain)^d K288T (HD domain)^d	N.A.	N.A.	[17, 19, 58]
Cutaneous T-cell lymphoma	N.A.	N.A.	Promoter DNA methylation	Reduced SAMHD1 mRNA and protein	[20]
Glioblastoma	0.3 %^c (1/290 cases)	N.A.	N.A.	N.A.	[15]
Lung cancer	1.7 %^c (4/228 cases)	A441T (HD domain)^d	Promoter DNA methylation	Reduced SAMHD1 mRNA and protein	[14, 21]
Myeloma	1 %^c (2/205 cases)	Y521D (HD domain)^d	N.A.	N.A.	[18]
Pancreatic cancer	1.1 %^c (1/91 cases)	N.A.	N.A.	N.A.	[12]

N.A. Information not available
^aThe mutation details are based on cited literature
^bIt is unclear whether all of these mutations in the HD domain of SAMHD1 can directly affect its dNTPase function
^cThe mutation rates are based on TCGA data analysis via cBioportal (http://www.cbioportal.org/public-portal/) [67]
^dThe amino acid (aa) changes and their positions; the sterile alpha motif (SAM) domain (aa 45-110); the catalytic region (aa 167-311) of the histidine-aspartate (HD) domain (aa 115-562) [68]

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