. 2018 Sep 6;9(9):912. doi: 10.1038/s41419-018-0919-9

Table 1.

Lineage specific master transcription factors, coactivators and corepressors of various tissues and identified genetic alterations in human malignancies

Tissue (n - TCGA)	Master transcription factor	Alteration frequency in TCGA database	Uniprot predicted coactivators	Alteration frequency in TCGA database	Uniprot predicted corepressors (http://www.uniprot.org/)	Alteration frequency in TCGA database
Liver (n = 442)	GATA4 ^6, 119	67% Hetloss	ARID1A	44% Hetloss, fs*	KDM1B	42% Amp, Gain
			ARID2	17% Hetloss, fs*	BAZ1B
	FOXA1 ¹²⁰	3% Amp Gain	KMT2A	28% Hetloss, fs*	SUZ12	32% Amp, Gain
			SMARCA4	24% Hetloss, fs*	DNMT1
	FOXA2 ¹²⁰	30% Amp Gain	SMARCAD1	46% Hetloss	BAZ2A	25% Amp, Gain
						15% Amp, Gain
						14% Amp, Gain
Pancreas (n = 109)	GATA4 ¹²¹	49% Hetloss	ARID1A	49% Hetloss, fs*	BAZ1B	57% Amp, Gain
			ARID1B	61% Hetloss	DNMT1
	GATA6 ¹²¹	23% Hetloss	ARID3C	43% Hetloss	UHRF1	50% Amp, Gain
			SMARCD1	50% Hetloss	SUZ12
	PTF1A ¹²²	20% Hetloss	SMARCB1	34% Hetloss	BAZ2A	45% Amp, Gain
	FOXA2 ¹²³	43% Amp Gain				40% Amp, Gain
	PDX1	58% Hetloss				39% Amp, Gain
Ovary (n = 302)	GATA4 ⁸³	69% Hetloss	ARID3A	91% Hetloss	EZH2	38% Gain amp
			ARID3B	50% Hetloss	DNMT1	39% Gain amp
	FOXL1/2 ^82, 87	67% Amp, Gain	ARID3C	37% Hetloss	BAZ1A	18% Gain amp
			SMARCAD1	68% Hetloss	EED	39% Gain amp
	FOXO1 ¹²⁴	63% Hetloss	ARID1B	67% Hetloss
			ARID1A	44% Hetloss
			SMARCA1	47% Hetloss

We analyzed TCGA data in cBioPortal to determine genetic alterations in genes mediating differentiation pathways. Lineage specific transcription factors were identified using lineage tracing studies. Cofactors interacting with lineage specific transcription factors were determined using data deposited in UniProt database (http://www.uniprot.org/). Master transcription factors are lineage specific and they recruit various coactivators to cooperate and turn on differentiation genes. While heterozygous loss of GATA4 and inactivation by frameshift mutations of GATA4 coactivators are frequent in hepatocellular carcinoma, other master transcription factors such as FOXA1 are available to mediate differentiation pathways. However, corepressors such as KDM1B, which are also recruited by these TFs, are aberrant in HCC by copy number gains and amplification. Such alterations impair ability for differentiation to ensue in HCC through epigenetic suppression of target genes^{5, 88, 89}. These forms of alterations are commonly observed also in PDAC, and OVC. Since corepressors are either gained or amplified in cancer but not inactivated by frameshift mutations, inhibition of these enzymes may serve as logical molecular targets of therapy (Fig. 5c, d)

*Frameshift mutation; hetloss, heterozygous deletion