Infrequent frameshift mutations of polynucleotide repeats in multiple primary cancers affecting the esophagus and other organs.
Frequent frameshift mutations of simple nucleotide repeats in the protein-encoding regions, as well as replication errors (RERs) at microsatellite loci, have recently been demonstrated in gastrointestinal tumors. These genetic instabilities have been considered indicative of an increased risk of accumulating mutations in cancer-associated genes and of developing multiple cancers. We studied frameshift (or insertion/deletion) mutations of simple nucleotide repeats in five genes (TGFbeta type II receptor [TGFbetaRII], E2F4, MSH2, MSH3, and MSH6) in 23 tumors from 12 patients who had synchronous cancers of the esophagus and other organs. Genetic instability at four microsatellite loci, as well as mutations in the TP53, APC, and KRAS2 genes, were also studied. No frameshift mutations were observed in the TGFbetaRII, MSH3, and MSH6 genes. RER and a deletion mutation of BAT26 in MSH2 were present in one (1/23; 4%) gastric cancer. This tumor also carried a deletion mutation in the serine (AGC) repeat of the E2F4 gene. Mutation screening of the TP53, APC, and KRAS2 genes revealed that the synchronous cancers did not carry the same mutations. Our results suggested that genetic instability, such as insertion/deletion mutations in simple nucleotide repeats, is not significantly associated with the development of multiple primary cancers of the esophagus and other organs, and that these synchronous cancers developed independently according to their different environmental factors.
Iwaya
T
T
Department of Pathology, Iwate Medical University School of Medicine, Morioka, Japan.
Maesawa
C
C
Nishizuka
S
S
Suzuki
Y
Y
Sakata
K
K
Sato
N
N
Ikeda
K
K
Koeda
K
K
Ogasawara
S
S
Otsuka
K
K
Kimura
Y
Y
Aoki
K
K
Ishida
K
K
Saito
K
K
Tamura
G
G
D003110:Colonic Neoplasms / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D051718:MutS Homolog 2 Protein; D000074081:MutS Homolog 3 Protein; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D051718:MutS Homolog 2 Protein; D000074081:MutS Homolog 3 Protein; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta; C094443:G-T mismatch-binding protein; C078444:MSH3 protein, human; C497172:MSH2 protein, human; C421109:multidrug resistance-associated protein 1