Chromosome allele loss in colorectal liver metastases and its association with clinical features

Ding, Shi-Fa; Delhanty, Joy D. A.; Zografos, George; Michail, Nagy E.; Dooley, JS; Na, Habib

doi:10.1002/bjs.1800810627

Cited by 17 publications

(8 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These tumours display distinctive clinicopathological features, including a tendency to be located in the right colon, associations with other neoplasms, a younger age at presentation, a high grade or medullary type, mucinous differentiation, and peritumoural ('Crohn's like') lymphoid infiltration. MSI status is also associated with an earlier stage at presentation and less nodal involvement compared with MSS tumours (25).…”

Section: Discussionmentioning

confidence: 94%

The incidence of mismatch repair gene defects in colorectal liver metastases

Alvarado-Bachmann

Smith

Gundara

et al. 2014

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. Knowledge of the molecular biology of primary colorectal cancer (CRC) has improved in recent years, and one reason for this is the identification of microsatellite instability (MSI), which occurs in up to 15% of sporadic CRC. However, less is known regarding the processes involved in colorectal liver metastases (CRLM). Increasing numbers of patients with CRLM are suitable for curative resection, so the identification of molecular markers may improve patient selection. The aim of the present study was to characterise the incidence of MSI in resected CRLM. Fifty-one sequentially resected CRLM specimens were selected. Clinicopathologic data was collated and immunohistochemistry for MLH1 and MSH2 was performed on paraffin sections of the CRLM specimens. The association between abnormal staining and the clinicopathological data was examined. The median age of the subjects in the current study was 65 years, the average number of CRLM was 2 and the median overall survival time was 42.1 months post liver resection. None of the 50 resected specimens demonstrated abnormal staining for MLH1 or MSH2. Compared with the previously reported incidence of MSI in primary CRC, the low incidence of MSI in the current cohort of CRLM precludes its use as a marker for use in making clinical decisions regarding this condition.

show abstract

Section: Discussionmentioning

confidence: 94%

The incidence of mismatch repair gene defects in colorectal liver metastases

Alvarado-Bachmann

Smith

Gundara

et al. 2014

Molecular Medicine Reports

View full text Add to dashboard Cite

show abstract

“…Previous studies have consistently identified a higher frequency of liver metastases in CRC tumours displaying complex karyotypes (tumours with more than three chromosomal abnormalities) bearing a loss of heterozygosity in chromosomes 5q 35, 36, 14q 37, 17p 35, 36, 18q 32, 35, 36, and 22q 36; losses of chromosomes 8p (59%), 1p (56%), and 18p (48%); and gains/amplification of chromosomes 13q (48%), 7p (44%), 8q (44%), and 20q (85%)—including amplification of 20q13 (38%) 32, 35. In agreement with these observations, all of our metastatic tumours showed complex karyotypes with seven or more altered chromosomes; at the same time, additional abnormalities were also observed in metastatic tumours for a large number of the above chromosomes (chromosomes 3, 7, 8, 9, 13, 17, and 20 in the whole series, and chromosomes X and Y in males).…”

Section: Discussionmentioning

confidence: 99%

Intratumoural cytogenetic heterogeneity of sporadic colorectal carcinomas suggests several pathways to liver metastasis

Sayagués

Abad

Melchor

et al. 2010

The Journal of Pathology

View full text Add to dashboard Cite

Much has been learned about the chromosomal abnormalities of colorectal carcinomas but the cytogenetic relationship between the neoplastic clones present in primary versus metastatic tumour samples remains unclear. We analyse the frequency of abnormalities for 47 chromosome regions using the interphase fluorescence in situ hybridization technique in a group of 48 tumours, including 24 primary colorectal tumours and 24 paired liver metastases. All tumours showed complex karyotypes with numerical/structural abnormalities for seven or more different chromosomes/chromosome regions both in the primary tumours and in their paired metastases. Chromosome 8 was the most frequently altered (22/24 primary tumours), consistently showing del(8p22) and/or gains/amplification of 8q24, followed by abnormalities of the entire chromosome 7 (21/24 primary tumours) and of chromosomes 17p and 20q (20/24 primary tumours). Simultaneous staining for multiple chromosome probes revealed the presence of two or more tumour cell clones in 23/24 cases (46/48 tumour samples). Interestingly, the liver metastases typically contained tumour cell clones similar to those found in the primary tumours, suggesting the absence of selective selection of specific tumour clones. Despite this, additional chromosomal abnormalities were detected in 23/24 metastatic tumours, which preferentially consisted of del(17p13) and gains/amplification of 11q13 and 20q13; moreover, compared to primary tumours, metastases showed an increased number of abnormalities of chromosomes 1p, 7q, 8q, 13q, and 18q, and new chromosomal abnormalities involving chromosomes 6, 10q23, 14q32, 15q22, and 19q13. Owing to the high frequency of numerical abnormalities of the entire chromosome 7 and loss and/or gain/amplification of specific regions of chromosome 8, eg del(8p22) and/or gains/amplification of 8q24 in primary colorectal tumours with associated metastases, it is suggested that their assessment at diagnosis could be of great clinical utility for the identification of colorectal cancer patients at higher risk of developing liver metastases.

show abstract

“…12 Three candidate tumor-suppressor genes, DCC, DPC4 and JV181, are located in this region. 20,21 Loss of 18q is associated with poor clinical outcome or metastases in colorectal cancer [22][23][24] and cervical squamous-cell carcinoma. 25 Chromosome arm 8q23-24 contains the candidate gene C-MYC, whose activation is a common event in various types of neoplasia and has been associated with different cellular processes relevant to the transformation of cancer cells to malignancy.…”

Section: Discussionmentioning

confidence: 99%

Chromosomal aberrations in colorectal cancers and liver metastases analyzed by comparative genomic hybridization

et al. 2001

View full text Add to dashboard Cite

Comparative genomic hybridization (CGH) was used to screen for changes in the number of DNA sequence copies in 30 primary colorectal cancers and 16 liver metastases, to identify regions that contain genes important for the development and progression of colorectal cancer. In primary colorectal cancer, we found frequent gains at 7p21 (36.7%), 7q31-36 (30%), 8q23-24 (43.0%), 12p (30%) Many detailed reports have been published on the carcinogenesis of colorectal cancer. Several genetic aberrations are required for tumor initiation and progression. 1 These aberrations include activation of the SRC and RAS oncogenes 2,3 along with inactivation of the FAP 4,5 and DCC 6 tumor suppressors and loss of TP53 function. 7 However, genetic changes involved in the progression and metastases of colorectal cancer remain unclear. To investigate differences in chromosomal aberrations between primary colorectal cancer and metastatic liver tumor, we used comparative genomic hybridization (CGH). CGH is based on dual-color fluorescence in situ hybridization (FISH) using differentially labeled tumors and reference DNA as a probe. 8,9 The efficacy of CGH is based on the concept that regions with an increase in the number of copies reveal sites that may contain dominantly acting oncogenes, whereas regions with a reduction may harbor putative tumorsuppressor genes. 8 Our aim was to generate a comprehensive picture of genomic and chromosomal aberrations that occur during the development of metastases of colorectal cancers and to identify those chromosomal regions that contain genes important for the development and progression of colorectal cancer.,Colorectal adenoma and adenocarcinoma have previously been analyzed by CGH, 10 as have primary and metastatic liver tumors. 11,12 These results supported ours; above all, we emphasize that some important genes appear to be contained in 20q and to play an important role in liver metastases. Furthermore, we examined the follow-up surveys of all cases and compared cases with and without loss at 18q and with gains at 8q and 20q to determine the usefulness of these genetic alterations as prognostic markers. MATERIAL AND METHODS Samples and DNA preparationPrimary tumors and metastatic liver tumors from 44 cancer patients with colorectal cancer (Table I) were classified according to the UICC system. These samples were provided by the Department of Digestive Surgery, Kyoto Prefectural University of Medicine (Kyoto, Japan). After surgical resection, tissues were frozen and stored at -80°C and DNA was extracted. CGHCGH was performed as described previously. 13 In brief, tumor DNA was labeled with FITC-dUTP and controlled DNA and extracted from a normal male with the aid of Texas red-dUTP using nick translation. Metaphase spreads were denatured at 75°C for 2.1 min in a formamide solution [70% formamide, 2 ϫ SCC (pH 7.0)] and dehydrated in an ethanol series of 70%, 85% and 100%. Labeled tumor and normal DNAs together with 10 g unlabeled cot-1 DNA was mixed with 50% formamide, 10% dextran sulfate and 2 ϫ SSC...

show abstract

Chromosome allele loss in colorectal liver metastases and its association with clinical features

Cited by 17 publications

References 30 publications

The incidence of mismatch repair gene defects in colorectal liver metastases

The incidence of mismatch repair gene defects in colorectal liver metastases

Intratumoural cytogenetic heterogeneity of sporadic colorectal carcinomas suggests several pathways to liver metastasis

Chromosomal aberrations in colorectal cancers and liver metastases analyzed by comparative genomic hybridization

Contact Info

Product

Resources

About