TY - JOUR
T1 - Three Classes of Genes Mutated in Colorectal Cancers with Chromosomal Instability
AU - Wang, Zhenghe
AU - Cummins, Jordan M.
AU - Shen, Dong
AU - Cahill, Daniel P.
AU - Jallepalli, Prasad V.
AU - Wang, Tian Li
AU - Parsons, D. Williams
AU - Traverso, Giovanni
AU - Awad, Mark
AU - Silliman, Natalie
AU - Ptak, Janine
AU - Szabo, Steve
AU - Willson, James K V
AU - Markowitz, Sanford D.
AU - Goldberg, Michael L.
AU - Karess, Roger
AU - Kinzler, Kenneth W.
AU - Vogelstein, Bert
AU - Velculescu, Victor E.
AU - Lengauer, Christoph
PY - 2004/5/1
Y1 - 2004/5/1
N2 - Although most colorectal cancers are chromosomally unstable, the basis for this instability has not been defined. To determine whether genes shown to cause chromosomal instability in model systems were mutated in colorectal cancers, we identified their human homologues and determined their sequence in a panel of colorectal cancers. We found 19 somatic mutations in five genes representing three distinct instability pathways. Seven mutations were found in MRE11, whose product is involved in double-strand break repair. Four mutations were found among hZw10, hZwilch/FLJ10036, and hRod/KNTC, whose products bind to one another in a complex that localizes to kinetochores and controls chromosome segregation. Eight mutations were found in Ding, a previously uncharacterized gene with sequence similarity to the Saccharomyces cerevisiae Pds1, whose product is essential for proper chromosome disjunction. This analysis buttresses the evidence that chromosomal instability has a genetic basis and provides clues to the mechanistic basis of instability in cancers.
AB - Although most colorectal cancers are chromosomally unstable, the basis for this instability has not been defined. To determine whether genes shown to cause chromosomal instability in model systems were mutated in colorectal cancers, we identified their human homologues and determined their sequence in a panel of colorectal cancers. We found 19 somatic mutations in five genes representing three distinct instability pathways. Seven mutations were found in MRE11, whose product is involved in double-strand break repair. Four mutations were found among hZw10, hZwilch/FLJ10036, and hRod/KNTC, whose products bind to one another in a complex that localizes to kinetochores and controls chromosome segregation. Eight mutations were found in Ding, a previously uncharacterized gene with sequence similarity to the Saccharomyces cerevisiae Pds1, whose product is essential for proper chromosome disjunction. This analysis buttresses the evidence that chromosomal instability has a genetic basis and provides clues to the mechanistic basis of instability in cancers.
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U2 - 10.1158/0008-5472.CAN-04-0587
DO - 10.1158/0008-5472.CAN-04-0587
M3 - Article
C2 - 15126332
AN - SCOPUS:2342557921
SN - 0008-5472
VL - 64
SP - 2998
EP - 3001
JO - Cancer research
JF - Cancer research
IS - 9
ER -