Cytogenetic aberrations and the role of telomer in carcinogenesis

1. Cytogenetic aberrations

Cytogenetics studies chromosome structure/function. Some cancer mutations are large enough to be visible on a karyotype (though some cancers have normal karyotypes).

Structural abnormalities

Type	Effect	Example
Balanced translocation	Even exchange, no net gain/loss; creates fusion gene or enhancer hijacking	t(9;22) BCR-ABL; t(14;18) BCL2
Deletion	Loss of tumor suppressor (needs both alleles lost)	13q14 → RB; 17p → p53
Gene amplification	Proto-oncogene overexpression	HER2, MYC, MDM2

Aneuploidy

• Abnormal chromosome number from a weakened mitotic checkpoint. Euploidy = exact multiple of haploid (n=23; 2n=46); anything else = heteroploidy.
• Monosomy (e.g. 45,X Turner), trisomy (13 Patau, 18 Edwards, 21 Down).

2. Telomeres and immortality

• Telomeres = repetitive end-cap sequences protecting chromosome ends from fusion. They shorten with each division → limited replicative capacity (Hayflick limit).
• Short telomeres are sensed by the DNA-repair system → p53/RB-mediated senescence.
• If p53/RB are mutated → checkpoints disabled → chromosome ends fuse → dicentric chromosomes → pulled apart in anaphase → new breaks: bridge-fusion-breakage (BFB) cycles → genomic instability + mitotic catastrophe.
• Cells that reactivate telomerase (TERT) (or use ALT) escape the crisis → with accumulated mutations → immortal malignant clone. Telomerase is normally active in stem cells, low/absent in somatic cells.

💡 High-yield: Structural lesions — balanced translocation (fusion), deletion (RB 13q14, p53 17p), amplification (HER2/MYC). Aneuploidy = weak mitotic checkpoint. Telomeres shorten each division; loss → p53/RB senescence; if checkpoints fail → BFB cycles → instability; tumors reactivate telomerase (TERT) for immortality.