Somatic mutation of the PTEN/MMAC1 gene in breast cancers with microsatellite instability

The extent to which microsatellite instability (MI) contributes to the etio logy of breast cancer has not been established in any large-scale studies. We examined 528 samples of tumor DNA from patients with primary breast canc er for MI, using 14 polymorphic CA-repeat markers. The frequency of MI in t hese tumors was unexpectedly low (10/528, 1.9%), The ten MI+ tumors were an alyzed for mutations in five potential target genes that contain simple rep eat sequences (TGFBIIR, IGF2R, hMSH6, BAX and PTEN/MMAC1), A somatic insert ion of an extra adenine in the (A)(6) region at codon 321-323 (exon 8) of t he PTEN/MMAC1 gene, leading to a frame-shift, was identified in one tumor. This observation represented the first documented instance of PTEN/MMAC1 al teration in a MI+ primary breast cancer. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.