Improved marker combination for detection of de novo genetic variation and aberrant DNA in colorectal neoplasia

Lisa Kann, James Han, David Ahlquist, Theodore Levin, Douglas Rex, Duncan Whitney, Sanford Markowitz, Anthony Shuber

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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 non-pathologic 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.

Original languageEnglish
Pages (from-to)2299-2302
Number of pages4
JournalClinical Chemistry
Volume52
Issue number12
DOIs
StatePublished - Dec 2006

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Adenoma
Colorectal Neoplasms
Tissue
Exons
Assays
DNA
Carcinoma
Neoplasms
Methylation
Genetic Heterogeneity
Genetic Markers
Tumors
Screening
Substitution reactions
Technology
Scanning
Polymerase Chain Reaction
Mutation

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Improved marker combination for detection of de novo genetic variation and aberrant DNA in colorectal neoplasia. / Kann, Lisa; Han, James; Ahlquist, David; Levin, Theodore; Rex, Douglas; Whitney, Duncan; Markowitz, Sanford; Shuber, Anthony.

In: Clinical Chemistry, Vol. 52, No. 12, 12.2006, p. 2299-2302.

Research output: Contribution to journalArticle

Kann, L, Han, J, Ahlquist, D, Levin, T, Rex, D, Whitney, D, Markowitz, S & Shuber, A 2006, 'Improved marker combination for detection of de novo genetic variation and aberrant DNA in colorectal neoplasia', Clinical Chemistry, vol. 52, no. 12, pp. 2299-2302. https://doi.org/10.1373/clinchem.2007.070896
Kann, Lisa ; Han, James ; Ahlquist, David ; Levin, Theodore ; Rex, Douglas ; Whitney, Duncan ; Markowitz, Sanford ; Shuber, Anthony. / Improved marker combination for detection of de novo genetic variation and aberrant DNA in colorectal neoplasia. In: Clinical Chemistry. 2006 ; Vol. 52, No. 12. pp. 2299-2302.
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abstract = "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 non-pathologic 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.",
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