Dataset Information

Local recurrences at the anastomotic area are clonally related to the primary tumor in sporadic colorectal carcinoma.

ABSTRACT: Anastomotic recurrences (AR) occur in 2-10% of colorectal carcinoma cases after resection of primary tumor (PT). Currently, there are no molecular data investigating their genetic profile and multiple theories exist about their pathogenesis. The aim of our study was to compare the genomic profile of AR to that of the patients' corresponding matched PT and, when available, to a distant metastasis (DM).Thirty-six tumors from 14 patients were genotyped using a capture-based, next-generation assay to define the mutational status of 341 cancer-associated genes. All patients had R0 resection of their PT and AR occurred 1.1-7.0 years following PT resection. A DM or a second AR was analyzed in 8 patients. All tumors were microsatellite stable except in one patient with Lynch syndrome.A total of 254 somatic mutations were detected including 138 mutations in the microsatellite stable (MSS) cases. The most commonly mutated genes were APC, KRAS, TP53, PIK3CA, ATM and PIK3R1. In all patients with MSS tumors the AR and PT shared between 50-100% of mutations, including mutations in key driver genes, consistent with these tumors being clonally related. Genetic events private to DM were not detected in AR and phylogenetic analysis showed that ARs were more closely related to PT than DM. In the Lynch syndrome patient the PT and AR showed distinct somatic mutations consistent with independent primaries.ARs are clonally related to PT in sporadic colorectal carcinomas and do not appear to represent seeding of the anastomotic site by distant metastases.

SUBMITTER: Vakiani E

PROVIDER: S-EPMC5522082 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Local recurrences at the anastomotic area are clonally related to the primary tumor in sporadic colorectal carcinoma.

Vakiani Efsevia E Shah Ronak H RH Berger Michael F MF Makohon-Moore Alvin P AP Reiter Johannes G JG Ostrovnaya Irina I Attiyeh Marc A MA Cercek Andrea A Shia Jinru J Iacobuzio-Donahue Christine A CA Solit David B DB Weiser Martin R MR

Oncotarget 20170601 26

<h4>Purpose</h4>Anastomotic recurrences (AR) occur in 2-10% of colorectal carcinoma cases after resection of primary tumor (PT). Currently, there are no molecular data investigating their genetic profile and multiple theories exist about their pathogenesis. The aim of our study was to compare the genomic profile of AR to that of the patients' corresponding matched PT and, when available, to a distant metastasis (DM).<h4>Experimental design</h4>Thirty-six tumors from 14 patients were genotyped us ...[more]

PMID: 28476018

Similar Datasets

Project description:BACKGROUND:Clinical and experimental evidence suggests that colorectal mucosal microbiota changes during colorectal carcinogenesis and may impair colorectal anastomotic wound healing. Thus, we hypothesized that amounts of colorectal cancer-associated microbes in colorectal tissue might be associated with anastomotic leakage after resection for colorectal carcinoma. METHODS:We analyzed 256 fresh frozen tissues of colorectal cancer from patients who underwent elective colorectal resection and anastomosis. Amounts of colorectal cancer-associated microbes, including Fusobacterium nucleatum, Escherichia coli possessing the polyketide synthase (pks) gene cluster, Enterococcus faecalis, and Bifidobacterium genus, in colorectal cancer tissues were measured by quantitative polymerase chain reaction assay; we equally dichotomized positive cases (high versus low). Multivariable logistic regression analysis was conducted to assess associations of these microbes with anastomotic leakage, adjusting for patient and tumor characteristics, and surgery-related factors. RESULTS:Fusobacterium nucleatum, pks-positive Escherichia coli, Enterococcus faecalis, and Bifidobacterium genus were detected in colorectal carcinoma tissue in 140 (54%), 94 (36%), 193 (75%), and 89 (35%) of 256 cases, respectively. Compared with Bifidobacterium genus-negative cases, Bifidobacterium genus-high cases were associated with an increased risk of anastomotic leakage (multivariable odds ratio, 3.96; 95% confidence interval, 1.50 to 10.51; Ptrend = 0.004). The association of Fusobacterium nucleatum, pks-positive Escherichia coli, or Enterococcus faecalis with anastomotic leakage was not statistically significant. CONCLUSIONS:The amount of Bifidobacterium genus in colorectal tissue is associated with an increased risk of anastomotic leakage after resection for colorectal cancer. These findings need to be validated to target gastrointestinal microflora for the prevention of anastomotic leakage after colorectal resection.

Project description:BackgroundBreast cancer is a leading cause of cancer-related death in women worldwide. Despite extensive studies in all areas of basic, clinical and applied research, accurate prognosis remains elusive, thus leading to overtreatment of many patients. Diagnosis could be improved by introducing multigene molecular scores in standard clinical practice. Several tests that work with formalin-fixed tissue have become routine. Molecular scores usually include several genes representing processes, response to oestrogens, progestogens and human epidermal growth factor receptor 2 (Her2), respectively, which are combined additively in single values. These multi-gene scores have the advantage of being more robust and reproducible than single-gene scores. Their utility may be further enhanced by combining them with classical diagnostic parameters. Here, we present an exploratory study comparing the RISK and research versions of Oncotype DX recurrence score (RS), Prosigna Risk of Recurrence (ROR) and EndoPredict (EP) with respect to their prognostic potential for ipsilateral recurrence and/or distant relapse in brain, and we compared the scores to the intrinsic subtypes based on PAM50.MethodsRNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue cores of primary tumours, local recurrences and brain metastases. Gene expression was measured on a NanoString nCounter Analysis System. Intrinsic subtypes and molecular scores were computed according to published literature and RISK, RS, ROR and EP were compared against each other and to the intrinsic subtypes Luminal A (lumA), Luminal B (lumB), Her2-enriched (Her2↑), Basal-like (basal), and Normal-like (normal) of PAM50. Local recurrences and brain metastases were compared to their corresponding primary tumours.ResultsAll four molecular scores were highly correlated. Highest correlations were observed among genes related to proliferation while lower correlations were found among oestrogen-related genes. The scores were significantly higher in primary tumours progressing to brain metastases as compared to recurrence-free primary tumours and primary tumours that relapsed as local recurrences.ConclusionsRISK and ROR-P are prognostic for primary tumours metastasizing to the brain. All four scores, RISK, RS, EP and ROR-P failed to discriminate between primary tumours that remained recurrence-free and primary tumours relapsing as local recurrences.

Dataset Information

Local recurrences at the anastomotic area are clonally related to the primary tumor in sporadic colorectal carcinoma.

Publications

Local recurrences at the anastomotic area are clonally related to the primary tumor in sporadic colorectal carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets