INFREQUENT CDKN2 (MTS1 P16) GENE ALTERATIONS IN HUMAN PRIMARY BREAST-CANCER/

Changes which lead to excessive cyclin production or to loss of cell c ycle inhibition by proteins such as p16/MTS1 may release breast tumour cells from the constraints of cell division. In order to establish th e frequency of MTS1/p16 gene alteration and its relation with genetic damage to the p53 and cyclin D1 genes, we have studied these gene abno rmalities in 164 human primary breast cancers and in six breast cancer cell lines. Two breast cancer cell lines and one primary tumour showe d a homozygous deletion of exon 2 of the MTS1 gene. Using single-stran d conformation polymorphism and subsequent sequencing analysis, one tu mour showed an alteration at codon 67 (CCC-->CTC; Pro to Leu). Another tumour showed a mutation at codon 98 (without amino acid change) with an additional polymorphism at codon 140. This polymorphism was also f ound in 13 other tumour samples, but has no effect on (disease-free) s urvival. From these data we conclude that the occurrence of CDKN2 (p16 /MTS1) mutation in primary breast cancer is a rare event and is not li kely to be involved in human breast tumour carcinogenesis and progress ion.