Fig. 3. Genetic alterations in lineage specifying master transcription factors in human malignancies.

a Analysis of TCGA data deposited in cBioPortal to determine alterations of master transcription factors of various lineages (Table 1). Key lineage specifying transcriptions factors were mostly haploinsufficient (heterozygous deletion/hetloss) in malignant cells or contained frequent amplification and gains. None of the transcription factors had biallelic frameshift inactivating mutations. Thus stalled differentiation occurs through genetic haploinsuffiency of key lineage specific transcription factors⁶. b Analysis of FOXL1 deletions across varying degrees of differentiation grades (pathological grades) of ovarian cancer. c Analysis of GATA4 deletions across varying degrees of differentiation grades of pancreatic cancer (PDAC). d Analysis of GATA deletions across varying degrees of differentiation grades liver cancer (HCC)