The novel germline mutation of the hMLH1 gene in a case of suspected hereditary non-polyposis colorectal cancer (HNPCC) in a patient with no family history of cancer.
Hereditary non-polyposis colorectal cancer (HNPCC) is a very important clinical entity in oncology. In order to identify HNPCC, the international diagnostic criteria, named 'Amsterdam criteria', has been used. In this report, we present a patient with HNPCC who completely lacks a family history of cancer, thus does not meet the revised Amsterdam criteria and was finally confirmed as HNPCC by genetic testing which revealed a novel germline mutation of the hMLH1 gene. The proband was a 52-year-old Japanese female with a diagnosis of advanced ascending colon cancer. She had a past history of Miles' operation for rectal cancer at the age of 40. A subtotal colectomy was performed and the subsequent microsatellite instability (MSI) analysis revealed high MSI in the resected tumor tissue. PCR/direct sequencing analysis of the genomic DNA revealed the base deletion 2006delAAAAG at codon 669 in exon 18 of the hMLH1 gene, which was considered to be a pathogenic mutation. According to the Human Mutation Database and International Collaborative Group on HNPCC (ICG-HNPCC) Database, this is the first report of this type of deletion mutation in the hMLH1 gene.
Tomita
Naohiro
N
Department of Surgery, Kansai Rosai Hospital, Amagasaki, Hyogo 660-8511, Japan. ntomita@kanrou.net
Fukunaga
Mutsumi
M
Okamura
Shu
S
Nakata
Ken
K
Ohzato
Hiroki
H
Tamura
Shigeyuki
S
Sugimoto
Keishi
K
Aihara
Tomohiko
T
Miki
Hirofumi
H
Takatsuka
Yuuichi
Y
Matsuura
Nariaki
N
Ishikawa
Hideki
H
Iwanaga
Takeshi
T
Fukayama
Noriko
N
Sugano
Kokichi
K
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003110:Colonic Neoplasms / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1