ETV6

ETV6 or ETS variant 6 is a gene that is located on chromosome 12 in humans. This gene is part of the ETS family of transcription factors, which are responsible for regulating a variety of cellular functions, including cell growth, differentiation, and apoptosis. Mutations in the ETV6 gene have been associated with a variety of hematological malignancies, including acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), and chronic myelomonocytic leukemia (CMML).

Structure

The ETV6 gene is composed of eight exons and spans approximately 275 kilobases on chromosome 12p13. The gene encodes a protein of 452 amino acids, which contains an ETS DNA-binding domain and a pointed (PNT) domain. The PNT domain is involved in protein-protein interactions, while the ETS domain binds to specific DNA sequences to regulate gene expression.

Function

ETV6 is a transcriptional repressor that plays a crucial role in hematopoiesis, the process by which blood cells are formed. It is expressed in hematopoietic stem cells and progenitor cells, and its expression decreases as these cells differentiate into mature blood cells. ETV6 regulates the expression of genes involved in cell proliferation, differentiation, and apoptosis, thereby maintaining the balance between cell growth and death.

Clinical Significance

Mutations in the ETV6 gene have been implicated in a variety of hematological malignancies. These mutations often result in the formation of fusion genes, which produce chimeric proteins with altered function. For example, the ETV6-RUNX1 fusion gene is the most common genetic alteration in childhood ALL, while the ETV6-NTRK3 fusion gene is associated with infantile fibrosarcoma and secretory breast carcinoma.

In addition to hematological malignancies, ETV6 mutations have also been identified in several solid tumors, including thyroid cancer, lung cancer, and colorectal cancer. These findings suggest that ETV6 may play a broader role in tumorigenesis beyond hematopoiesis.

See Also

• ETS family
• Hematopoiesis
• Acute lymphoblastic leukemia
• Myelodysplastic syndrome
• Chronic myelomonocytic leukemia