title: Analysis of K-ras, BRAF, and PIK3CA mutations in laterally-spreading tumors of the colorectum.
abstract: OBJECTIVE
  Laterally-spreading tumors (LST) are a newly-recognized category of colorectal neoplasia, and are defined as lesions larger than 10 mm in diameter and extending circumferentially rather than vertically. However, genetic features of this new category of tumors are not fully elucidated. The aim of this study was to evaluate genetic alterations in LST.
  
  
  METHODS
  We examined K-ras, BRAF, and phosphoinositide-3-kinase catalytic-α polypeptide (PIK3CA) mutations in 101 LST, including 68 LST-granular type (LST-G) and 33 LST-non-granular type by direct sequencing. As controls, we examined these gene mutations in 66 protruded colon adenomas (10 mm or larger) and 44 advanced colon cancers.
  
  
  RESULTS
  K-ras, BRAF, and PIK3CA mutations were observed in 59 (58%), zero (0%), and three (3%) LST, respectively. LST-G morphology in the right-sided colon was significantly correlated with the existence of K-ras mutations, whereas a size of 20 mm or larger was the only predictor of mutations in the left-sided colorectum. The frequency of K-ras mutations in LST was particularly marked in the left-sided colorectum compared to protruded adenomas or advanced cancers (LST vs protruded adenomas, P < 0.001; LST vs advanced cancers, P = 0.002), whereas in the right-sided colon, K-ras mutations were equally frequent. PIK3CA mutations were not familiar in either LST (3%) or advanced cancers (9%).
  
  
  CONCLUSIONS
  K-ras mutations were involved in colorectal LST in different manners according to tumor location.
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Kaji
authors.forename: Jun
authors.initials: J
authors.lastname: Kato
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Akita
authors.forename: Joichiro
authors.initials: J
authors.lastname: Horii
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Saito
authors.forename: Reiji
authors.initials: R
authors.lastname: Higashi
authors.forename: Shin
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Motoaki
authors.initials: M
authors.lastname: Kuriyama
authors.forename: Sakiko
authors.initials: S
authors.lastname: Hiraoka
authors.forename: Toshio
authors.initials: T
authors.lastname: Uraoka
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000236:Adenoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000368:Aged; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D016017:Odds Ratio; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018570:Risk Assessment; D012307:Risk Factors; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins