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

Verified step by step guidance

1. Understand that a translocation is a chromosomal abnormality where a segment of one chromosome breaks off and attaches to another chromosome, potentially disrupting normal gene function.
2. Recognize that the Philadelphia chromosome is a specific translocation between chromosomes 9 and 22, denoted as t(9;22)(q34;q11), which fuses parts of two genes: BCR from chromosome 22 and ABL from chromosome 9.
3. Learn that this fusion creates a novel BCR-ABL gene that encodes a constitutively active tyrosine kinase enzyme, which means it is always 'on' and continuously signals cells to divide.
4. Understand that this uncontrolled signaling leads to increased cell proliferation and reduced apoptosis (programmed cell death), contributing to the development of cancer, specifically chronic myelogenous leukemia (CML).
5. Summarize that translocations like the Philadelphia chromosome contribute to cancer by creating abnormal fusion genes that produce proteins disrupting normal cell cycle regulation and promoting malignant transformation.

Key Concepts

Chromosomal Translocations

Chromosomal translocations occur when segments from two different chromosomes break and reattach to each other. This rearrangement can disrupt normal gene function or create novel gene fusions, which may alter cellular behavior. Translocations are a common genetic abnormality in various cancers.

Philadelphia Chromosome

The Philadelphia chromosome is a specific translocation between chromosomes 9 and 22, producing the BCR-ABL fusion gene. This abnormal gene encodes a constitutively active tyrosine kinase that drives uncontrolled cell division, primarily associated with chronic myeloid leukemia (CML).

Oncogene Activation and Cancer Development

Oncogenes are mutated or abnormally expressed genes that promote cancer. Translocations can activate oncogenes by creating fusion proteins or misregulating gene expression, leading to increased cell proliferation and survival. This process is a key mechanism by which genetic changes contribute to cancer.