How do translocations such as the Philadelphia chromosome contribute to cancer?

Key Concepts

Translocation

Translocation is a genetic alteration where a segment of one chromosome breaks off and attaches to another chromosome. This can disrupt normal gene function and lead to the formation of fusion genes, which can produce abnormal proteins that drive uncontrolled cell growth, a hallmark of cancer.

Philadelphia Chromosome

The Philadelphia chromosome is a specific genetic abnormality resulting from a translocation between chromosomes 9 and 22. This translocation creates the BCR-ABL fusion gene, which encodes a tyrosine kinase that promotes cell proliferation and inhibits apoptosis, contributing to the development of chronic myeloid leukemia (CML).

Oncogenes

Oncogenes are mutated forms of normal genes (proto-oncogenes) that, when activated, can lead to cancer. The BCR-ABL fusion gene acts as an oncogene by continuously signaling cells to divide, bypassing the normal regulatory mechanisms, thus playing a critical role in the oncogenesis associated with the Philadelphia chromosome.