Searching for microsatellite mutations in coding regions in lung, breast, ovarian and colorectal cancers.
RepX represents a new informatics approach to probe the UniGene database for potentially polymorphic repeat sequences in the open reading frame (ORF) of genes, 56% of which were found to be actually polymorphic. We now have performed mutational analysis of 17 such sites in genes not found to be polymorphic (<0.03 frequency) in a large panel of human cancer genomic DNAs derived from 31 lung, 21 breast, seven ovarian, 21 (13 microsatellite instability (MSI)+ and eight MSI-) colorectal cancer cell lines. In the lung, breast and ovarian tumor DNAs we found no mutations (<0.03-0.04 rate of tumor associated open reading frame mutations) in these sequences. By contrast, 18 MSI+ colorectal cancers (13 cancer cell lines and five primary tumors) with mismatch repair defects exhibited six mutations in three of the 17 genes (SREBP-2, TAN-1, GR6) (P<0.000003 compared to all other cancers tested). We conclude that coding region microsatellite alterations are rare in lung, breast, ovarian carcinomas and MSI (-) colorectal cancers, but are relatively frequent in MSI (+) colorectal cancers with mismatch repair deficits.
Forgacs
E
E
The Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, TX 75390-8593, USA.
Wren
J D
JD
Kamibayashi
C
C
Kondo
M
M
Xu
X L
XL
Markowitz
S
S
Tomlinson
G E
GE
Muller
C Y
CY
Gazdar
A F
AF
Garner
H R
HR
Minna
J D
JD
D020137:Base Pair Mismatch; D001943:Breast Neoplasms / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D016208:Databases, Factual; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics*; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D012984:Software