isochromosome

An isochromosome is a chromosome in which one arm is duplicated and the other arm is missing, resulting in a chromosome with two identical arms. Isochromosomes arise by misdivision of the centromere during cell division, producing a chromosome composed of two copies of either the short arm (p) or the long arm (q).

The presence of an isochromosome causes a copy number imbalance: the arm represented on the isochromosome is present in two copies on that chromosome while the opposite arm is lost on that chromosome. Depending on the normal chromosome complement, this can produce partial trisomy of one arm and partial monosomy of the other, leading to developmental abnormalities in constitutional cases or to altered gene dosage in somatic cells, such as in tumors.

Several isochromosomes have been described. A well-established example is isochromosome 12p (i(12p)), frequently observed as a marker in testicular germ cell tumors and associated with amplification of 12p. Isochromosomes involving other chromosomes, including 18 and X, have also been reported in various constitutional and neoplastic contexts.

Detection and characterization rely on cytogenetic and molecular methods, including conventional karyotyping, fluorescence in situ hybridization (FISH), and array-based comparative genomic hybridization or SNP arrays. These techniques help determine the specific arm duplicated and the extent of accompanying chromosomal imbalance.

Clinical significance varies by chromosome and tissue. In constitutional cases, isochromosomes can contribute to developmental delay, dysmorphism, or mosaic syndromes. In cancer, they can drive tumor progression by altering the dosage of oncogenes or tumor suppressor genes.