Genetic analysis of radiation-associated rectal cancer.
Genetic aberrations in radiation-associated colorectal cancer have not been studied in detail. We analyzed genetic aberrations in five rectal cancers that developed long after radiotherapy had been performed for cervical cancer. Microsatellite instability (MSI) in tumors was examined at five loci: D2S123, D3S966, TP53, DCC, and BAT26. Mutation of simple repeat sequences within the hMSH3, BAX, and transforming growth factor Beta type II receptor ( TGFBetaRII) genes was examined by polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP). Mutation of p53 exons 5-8 was examined by PCR-SSP and direct sequencing. Mutations of the K- ras gene were analyzed by two-step PCR. No MSI was found in tumor specimens at any of the loci examined, and no mutations in the target genes were observed. K- ras mutation was detected in two carcinomas, but not in their irradiated normal mucosa, while p53 mutation was observed in another two carcinomas, but not in their irradiated normal mucosa. Our results suggest that the radiation-associated rectal carcinomas examined in this study did not develop through the mutator phenotype pathway; rather, tumorigenesis was probably mediated through the multistep carcinogenesis pathway.
Tsuji
Takashi
T
Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, 852-8501 Nagasaki, Japan.
Sawai
Terumitsu
T
Nakagoe
Tohru
T
Hidaka
Shigekazu
S
Shibasaki
Shinichi
S
Tanaka
Kenji
K
Nanashima
Atsushi
A
Yamaguchi
Hiroyuki
H
Yasutake
Tohru
T
Tagawa
Yutaka
Y
D000368:Aged; D005260:Female; D006801:Humans; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000532:radiotherapy; D011878:Radiotherapy / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000235:genetics*