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TY - JOUR AU - Lengauer, C. AU - Kinzler, K. W. AU - Vogelstein, B. PY - 1997 DA - 1997/04/01 TI - Genetic instability in colorectal cancers JO - Nature SP - 623 EP - 627 VL - 386 IS - 6625 AB - It has long been considered that genetic instability is an integral component of human neoplasia1–3. In a small fraction of tumours, mismatch repair deficiency leads to a microsatellite instability at the nucleotide sequence level4,5. In other tumours, an abnormal chromosome number (aneuploidy) has suggested an instability, but the nature and magnitude of the postulated instability is a matter of conjecture. We show here that colorectal tumours without microsatellite instability exhibit a striking defect in chromosome segregation, resulting in gains or losses in excess of 10 –2 per chromosome per generation. This form of chromosomal instability reflected a continuing cellular defect that persisted throughout the lifetime of the tumour cell and was not simply related to chromosome number. While microsatellite instability is a recessive trait6,7, chromosomal instability appeared to be dominant. These data indicate that persistent genetic instability may be critical for the development of all colorectal cancers, and that such instability can arise through two distinct pathways. SN - 1476-4687 UR - https://doi.org/10.1038/386623a0 DO - 10.1038/386623a0 ID - Lengauer1997 ER -