Counting alleles to predict recurrence of early-stage colorectal cancers

Zhou, Wei; Goodman, Steven N.; Galizia, Gennaro; Lieto, Eva; Ferraraccio, Francesca; Pignatelli, Carlo; Purdie, Colin A.; Piris, J; Morris, Robert; Harrison, David J.; Paty, Philip B.; Culliford, Al; Romans, Katharine; Montgomery, Elizabeth A.; Choti, Michael A.; Kinzler, Kenneth W.; Vogelstein, Bert

doi:10.1016/s0140-6736(02)07448-2

Cited by 137 publications

(98 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1). The sequential probability ratio test (SPRT) (16,18) (see below) was applied to determine whether the P r indicated the degree of allelic imbalance that would be expected for a T21 sample. Alternatively, the SPRT analysis may indicate that the available data are not yet adequate for disease classification.…”

Section: Resultsmentioning

confidence: 99%

Digital PCR for the molecular detection of fetal chromosomal aneuploidy

Lun²,

Chan³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

391

328

View full text Add to dashboard Cite

Trisomy 21 is the most common reason that women opt for prenatal diagnosis. Conventional prenatal diagnostic methods involve the sampling of fetal materials by invasive procedures such as amniocentesis. Screening by ultrasonography and biochemical markers have been used to risk-stratify pregnant women before definitive invasive diagnostic procedures. However, these screening methods generally target epiphenomena, such as nuchal translucency, associated with trisomy 21. It would be ideal if noninvasive genetic methods were available for the direct detection of the core pathology of trisomy 21. Here we outline an approach using digital PCR for the noninvasive detection of fetal trisomy 21 by analysis of fetal nucleic acids in maternal plasma. First, we demonstrate the use of digital PCR to determine the allelic imbalance of a SNP on PLAC4 mRNA, a placenta-expressed transcript on chromosome 21, in the maternal plasma of women bearing trisomy 21 fetuses. We named this the digital RNA SNP strategy. Second, we developed a nonpolymorphism-based method for the noninvasive prenatal detection of trisomy 21. We named this the digital relative chromosome dosage (RCD) method. Digital RCD involves the direct assessment of whether the total copy number of chromosome 21 in a sample containing fetal DNA is overrepresented with respect to a reference chromosome. Even without elaborate instrumentation, digital RCD allows the detection of trisomy 21 in samples containing 25% fetal DNA. We applied the sequential probability ratio test to interpret the digital PCR data. Computer simulation and empirical validation confirmed the high accuracy of the disease classification algorithm.circulating fetal nucleic acids ͉ noninvasive prenatal diagnosis ͉ sequential probability ratio test ͉ trisomy 21 ͉ RNA SNP

show abstract

Section: Resultsmentioning

confidence: 99%

Digital PCR for the molecular detection of fetal chromosomal aneuploidy

Lun²,

Chan³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

391

328

View full text Add to dashboard Cite

show abstract

“…This is consistent with recent digital SNP analysis. 8 Also, loss of both chromosomes 4 and 14q was associated with shorter disease-free survival probably indicates a selective advantage for tumours harbouring these losses. The precise molecular and cellular mechanisms behind such selection remain to be elucidated and await further refinement of these areas.…”

Section: Discussionmentioning

confidence: 99%

“…At the genomic level, few studies have focused on early-stage colorectal cancer [3][4][5][6] and of those studies that focused on early-stage colorectal cancer, the analysis was limited to few chromosomes. 7,8 Therefore, there is currently a need to profile primary tumours from early-stage colorectal cancer using genome-wide scanning techniques that can also be integrated into current laboratory practices. We describe here the first attempt to study early-stage colorectal cancer at the genomic level using genomewide scanning DNA methodologies and address the role of chromosomal aberrations in prognosis.…”

mentioning

confidence: 99%

Genetic profiling of stage I and II colorectal cancer may predict metastatic relapse

et al. 2006

View full text Add to dashboard Cite

A substantial number of patients with early-stage colorectal cancer relapse from metastatic disease. Identification of these patients by genetic profiling of their primary tumours may allow more informed followup and tailored administration of adjuvant therapy. Primary tumours from 70 patients with early-stage and largely microsatellite-stable colorectal cancer were profiled using metaphase-based comparative genomic hybridization (CGH) and the aberrations confirmed independently in a subset of patients using microarraybased CGH. Of the 70 cancers, 61 were amenable to CGH, and follow-up data was available from 56 patients. Genomic aberrations were correlated with patients' survival using univariate, multivariate and Kaplan-Meier survival curves. Metastatic primary tumours exhibited more complex genomic aberrations than non-metastatic primary tumours. Loss of chromosome 4p was an independent prognostic factor in early-stage colorectal cancer using multivariate analysis (Hazard ratio, 9.6; 95% CI, 3.3-28; P ¼ 0.0001). Loss of both chromosome arms 8p and 18q had a statistically significant negative effect on disease-free survival. Moreover, primary tumours with loss of both chromosomes 4 and 14q bestowed poorer prognosis than tumours with loss of any one of the two chromosomes (Po0.0001). Genetic profiling of primary tumours of patients with early-stage colorectal cancer is of significant value in identifying the subset of patients who may relapse with metastatic disease. Accordingly, the molecular genetic features of primary tumours should be considered in the mainstream management of patients with this specific stage of the disease.

show abstract

“…Genomic analyses of cancer samples, by cytogenetic studies and more recently by array-based profiling, have identified recurrent alterations associated with all investigated cancer types. [7][8][9][10][11] With respect to CRC, a few CNAs have been associated with outcome, [12][13][14] some have led to the identification of cancercausing genes, 15 and others have suggested potential therapeutic strategies. 16 Over the recent years, advances in genome characterization technologies have enabled increasingly systematic efforts to characterize genomic alterations in human cancer samples.…”

mentioning

confidence: 99%

Frequent genomic loss at chr16p13.2 is associated with poor prognosis in colorectal cancer

Andersen

Lamy

Thorsen

et al. 2011

Intl Journal of Cancer

View full text Add to dashboard Cite

Genomic alterations play important roles in colorectal cancer (CRC) carcinogenesis. Here, we aimed to identify and characterize recurrent copy-number alterations (CNAs) associated with clinical outcome of CRC by the use of single nucleotide polymorphism arrays, genomic quantitative PCR (qPCR) and fluorescence in situ hybridization (FISH). Colorectal neoplasia specimens and paired germline samples from 144 patients (40 adenomas and 104 carcinomas) as well as 40 CRC cell lines were investigated. This large dataset revealed frequent loss, including homozygous loss, at chr16p13.2 (from 5.9 to 7.42Mb). The loss was observed in 30% of adenomas and even more frequently in carcinomas, 56%, indicating that the loss define a subset of adenomas with a propensity for invasion. Consistent with this, the loss occurred twice as frequent in villous (40%) as in tubular adenomas (20%). The loss occurred independently of microsatellite stability and could be validated by qPCR in an independent sample cohort (n 5 71). In Stage II/III, microsatellite stable (MSS) CRC it was associated with poor recurrence free survival (hazard ratio 2.4; p 5 0.02; Multivariate Cox regression analysis). No transcriptional consequences of the losses were observed, and the only gene, A2BP1, located in the region showed no mutations. Correlation with other CNAs was established for chr3p22 in carcinomas and chr20p (inverse) in adenomas. FISH documented the chr16p13.2 region to be involved in complex structural rearrangements that included translocation to chr3p22 in some cases. The findings indicate that structural rearrangements involving chr16p13.2 are very frequent in colorectal neoplasia, often lead to homozygous deletion, and are associated with poor clinical outcome.Despite major efforts over the recent years toward improving the survival outcome of patients with colorectal cancer (CRC), the disease remains a major health burden with over one million cases worldwide and a disease-specific mortality of $33% in the developed world. 1 Currently, the gold standard for prognostication is clinicopathological staging, based on the Tumor, Node, Metastasis (TNM) classifcation. However. Although CRC is often diagnosed at a stage where complete resection of the primary cancer (Stages I-III) is possible, 40-50% of patients who undergo potentially curative surgery alone relapse and die of metastatic disease. 2 Although most patients with Stage III (lymph-node positive) cancer receive adjuvant treatment, it is offered to only a subset of Stage II (localized disease) patients presenting with specific high-risk clinical features, including tumor perforation or invasion of adjacent organs. 3 This approach is clearly suboptimal, resulting in undertreatment of $20% of Stage II patients who will recur. Similarly, current adjuvant treatment is clearly ineffective in many Stage III patients, with a recurrence rate of $40% 4,5 highlighting the need for treatment with more aggressive or newly emerging targeted therapies, e.g., inhibitors of epidermal growth factor recepto...

show abstract

Counting alleles to predict recurrence of early-stage colorectal cancers

Cited by 137 publications

References 26 publications

Digital PCR for the molecular detection of fetal chromosomal aneuploidy

Digital PCR for the molecular detection of fetal chromosomal aneuploidy

Genetic profiling of stage I and II colorectal cancer may predict metastatic relapse

Frequent genomic loss at chr16p13.2 is associated with poor prognosis in colorectal cancer

Contact Info

Product

Resources

About