BACKGROUND: The genetic heterogeneity of sporadic colorectal cancer (CRC) makes the choice of genetic markers and sequence variation-detection technologies critical to the performance of screening assays. We have previously described the effectiveness of a CRC assay composed of 22 known variants in KRAS, APC, TP53, and BAT-26 (V1). We introduce a new marker formulation (V2) that includes detection of de novo variation in APC, PIK3CA, and CTNNB1, hypermethylated sequences within SMARCA3 and VIM, and a single-base variation within BRAF. We compared the abilities of the V1 and V2 markers to detect aberrant DNA in colorectal neoplasias. METHODS: V1 and V2 marker formulations were used to analyze 144 colorectal tissue samples comprising 50 precancerous adenomas, 94 carcinomas, and 11 nonpathologic tissues. V1 analysis consisted of single-base extension analysis of the 22 V1 variants. V2 analysis consisted of DNA scanning of the APC mutation cluster region, PIK3CA exons 9 and 20, CTNNB1 exon 3, analysis for the BRAF Val600Glu substitution, and methylation-specific PCR analysis of VIM and SMARCA3. RESULTS: The V2 marker formulation had significantly higher sensitivity than the V1 markers for carcinomas (93.6% and 72.3%, respectively; P = 0.0002) and adenomas (92.0% and 62.0%, respectively; P = 0.0006). None of the nonpathologic samples were positive for any marker. CONCLUSIONS: We demonstrate improved sensitivity of a new marker formulation (V2) to detect aberrant DNA in CRC and precancerous adenoma tumor tissues.
BACKGROUND: The genetic heterogeneity of sporadic colorectal cancer (CRC) makes the choice of genetic markers and sequence variation-detection technologies critical to the performance of screening assays. We have previously described the effectiveness of a CRC assay composed of 22 known variants in KRAS, APC, TP53, and BAT-26 (V1). We introduce a new marker formulation (V2) that includes detection of de novo variation in APC, PIK3CA, and CTNNB1, hypermethylated sequences within SMARCA3 and VIM, and a single-base variation within BRAF. We compared the abilities of the V1 and V2 markers to detect aberrant DNA in colorectal neoplasias. METHODS: V1 and V2 marker formulations were used to analyze 144 colorectal tissue samples comprising 50 precancerous adenomas, 94 carcinomas, and 11 nonpathologic tissues. V1 analysis consisted of single-base extension analysis of the 22 V1 variants. V2 analysis consisted of DNA scanning of the APC mutation cluster region, PIK3CA exons 9 and 20, CTNNB1 exon 3, analysis for the BRAFVal600Glu substitution, and methylation-specific PCR analysis of VIM and SMARCA3. RESULTS: The V2 marker formulation had significantly higher sensitivity than the V1 markers for carcinomas (93.6% and 72.3%, respectively; P = 0.0002) and adenomas (92.0% and 62.0%, respectively; P = 0.0006). None of the nonpathologic samples were positive for any marker. CONCLUSIONS: We demonstrate improved sensitivity of a new marker formulation (V2) to detect aberrant DNA in CRC and precancerous adenoma tumor tissues.
Authors: Frank Diehl; Kerstin Schmidt; Kristine H Durkee; Kent J Moore; Steve N Goodman; Anthony P Shuber; Kenneth W Kinzler; Bert Vogelstein Journal: Gastroenterology Date: 2008-05-15 Impact factor: 22.682
Authors: David A Ahlquist; Daniel J Sargent; Charles L Loprinzi; Theodore R Levin; Douglas K Rex; Dennis J Ahnen; Kandice Knigge; M Peter Lance; Lawrence J Burgart; Stanley R Hamilton; James E Allison; Michael J Lawson; Mary E Devens; Jonathan J Harrington; Shauna L Hillman Journal: Ann Intern Med Date: 2008-10-07 Impact factor: 25.391
Authors: Árpád V Patai; Gábor Valcz; Péter Hollósi; Alexandra Kalmár; Bálint Péterfia; Árpád Patai; Barnabás Wichmann; Sándor Spisák; Barbara Kinga Barták; Katalin Leiszter; Kinga Tóth; Ferenc Sipos; Ilona Kovalszky; Zoltán Péter; Pál Miheller; Zsolt Tulassay; Béla Molnár Journal: PLoS One Date: 2015-08-20 Impact factor: 3.240
Authors: Yoko Ito; Thibaud Koessler; Ashraf E K Ibrahim; Sushma Rai; Sarah L Vowler; Sayeda Abu-Amero; Ana-Luisa Silva; Ana-Teresa Maia; Joanna E Huddleston; Santiago Uribe-Lewis; Kathryn Woodfine; Maja Jagodic; Raffaella Nativio; Alison Dunning; Gudrun Moore; Elena Klenova; Sheila Bingham; Paul D P Pharoah; James D Brenton; Stephan Beck; Manjinder S Sandhu; Adele Murrell Journal: Hum Mol Genet Date: 2008-06-09 Impact factor: 6.150