Somatic mutation of the PTEN/MMAC1 gene in breast cancers with microsatellite instability.
The extent to which microsatellite instability (MI) contributes to the etiology of breast cancer has not been established in any large-scale studies. We examined 528 samples of tumor DNA from patients with primary breast cancer for MI, using 14 polymorphic CA-repeat markers. The frequency of MI in these tumors was unexpectedly low (10/528, 1.9%). The ten MI+ tumors were analyzed for mutations in five potential target genes that contain simple repeat sequences (TGFBIIR, IGF2R, hMSH6, BAX and PTEN/MMAC1). A somatic insertion of an extra adenine in the (A)6 region at codon 321-323 (exon 8) of the PTEN/MMAC1 gene, leading to a frame-shift, was identified in one tumor. This observation represented the first documented instance of PTEN/MMAC1 alteration in a MI+ primary breast cancer.
Minobe
K
K
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan.
Bando
K
K
Fukino
K
K
Soma
S
S
Kasumi
F
F
Sakamoto
G
G
Furukawa
K
K
Higuchi
K
K
Onda
M
M
Nakamura
Y
Y
Emi
M
M
D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D025521:Tumor Suppressor Proteins
D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human