ZBTB7A
Overview
ZBTB7A (Zinc Finger and BTB Domain Containing 7A), also known as LRF (Leukemia/Lymphoma Related Factor), is a transcriptional repressor that controls B-cell differentiation and germinal center biology. In the integrative DLBCL genomic landscape study of 1001 patients, ZBTB7A emerged as a GCB-selective CRISPR essential dependency, identifying it as a functional oncogene in the GCB DLBCL context.
Alterations observed in the corpus
- ZBTB7A knockout was selectively lethal in GCB DLBCL cell lines but not ABC DLBCL in a genome-wide CRISPR screen (GeCKO v2, ~120,000 sgRNAs) across six lymphoma cell lines — identifying it as a GCB-selective functional oncogene PMID:28985567.
Cancer types (linked)
- DLBCLNOS — GCB-selective CRISPR essentiality in a genome-wide screen across six cell lines (3 ABC, 2 GCB, 1 Burkitt-like); supports a lineage-specific growth dependency in GCB DLBCL PMID:28985567.
Co-occurrence and mutual exclusivity
- ZBTB7A shares GCB-selective essentiality with XPO1, TGFBR2, and PTPN6 in DLBCL, suggesting these genes form a network of GCB-lineage dependencies PMID:28985567.
Therapeutic relevance
- GCB-selective CRISPR dependency implicates ZBTB7A as a candidate therapeutic target in GCB DLBCL; no direct drug targeting ZBTB7A is yet in clinical use, but its essentiality suggests synthetic-lethal or indirect targeting strategies may be of interest PMID:28985567.
Open questions
- The CRISPR screen was performed across only six cell lines, which may not fully represent GCB DLBCL heterogeneity; lethal effects of driver gene knockout were not restricted to cell lines harboring mutations in those genes, suggesting broadly favored proliferative pathways rather than strict synthetic-lethal vulnerabilities PMID:28985567.
Sources
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