Colorectal mucinous adenocarcinoma indicates a meaningful subtype: A whole genome sequencing study.
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ABSTRACT:
SUBMITTER: Xu Y
PROVIDER: S-EPMC10131291 | biostudies-literature | 2023 Apr
REPOSITORIES: biostudies-literature
Publications
Colorectal mucinous adenocarcinoma indicates a meaningful subtype: A whole genome sequencing study.
Xu Yunhua Y Chen Xiguang X Chen Yuqiao Y Wu Xiaofeng X Fang Qing Q Tan Xiangwen X Li Shuxiang S Huang Qiulin Q Zu Xuyu X Fu Kai K Xiao Shuai S
Clinical and translational medicine 20230401 4
Similar Datasets
Project description:IntroductionMucinous adenocarcinoma of the rectum is an infrequently encountered histological subtype that is associated with an impaired response to chemoradiotherapy and a worse overall prognosis. A genomic profile analysis of mucinous rectal tumors has not yet been performed. The aim of this study was to comprehensively describe the burden of somatic mutations and copy number variation as well as perform mutational signature and microbial analysis of an in-house collected cohort of mucinous adenocarcinoma of the rectum.MethodsGenomic DNA was extracted from 10 cases of mucinous rectal cancer and matched normal tissue. Whole genome sequencing (WGS) was carried out on these 10 cases and a comprehensive bioinformatic analysis was undertaken.ResultsThe average number of SNVs, InDels and SVs in the cohort was 16,600, 1,855, and 120, respectively. A single case was MSI-H. KRAS mutations were found in 70% of cases while TP53 was mutated in only 40% of cases. CNA gain was identified on chromosomes 7, 8, 12, 13, and 20 while CNA loss was found on chromosomes 4, 8, 17, and 18 corresponding to oncogenes and tumor suppressor genes, respectively. Overall mucinous rectal cancers are more likely to be MSI-H and to have KRAS, BRAF, and PIK3CA mutations when compared to rectal adenocarcinoma NOS. Microbial analysis demonstrated an abundance of Fusobacterium nucleatum in tumor samples compared to normal tissue.ConclusionThis study provides a detailed WGS analysis of 10 cases of mucinous rectal cancer. It demonstrates an important lesson in tumor biology in that histologically similar tumors can have extensive differences at the genomic level. This study is relevant as it raises important questions about the relationship between bacteria and malignancy.
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Project description:Mucinous colorectal adenocarcinoma
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Project description:This SuperSeries is composed of the SubSeries listed below.
2024-04-28 | GSE236698 | GEO
Project description:BackgroundAs a rare subtype of primary lung adenocarcinoma (LUAD), mucinous pulmonary adenocarcinoma (MPA) was considered a distinctive entity with unfavorable outcomes. Therefore, there is a great need for a better understanding of the genomic and immunological landscape of this rare tumor type, which would inform improved therapeutic strategies.MethodsA total of 96 patients histologically confirmed with MPA were recruited from Shandong Cancer Hospital and Institute (SCH). Single nucleotide variation (SNV), copy number variation (CNV), genomic instability, and immunological landscape insights into 96 MPA patients were identified using WES.ResultsWe demonstrated that MPAs had marked different genomic alterations and were more complex in genomic profiles than LUADs. Mutations in Tumor Protein 53 (TP53) and CYP7A Promoter-Binding Factor (CPF) pathways significantly shortened survival whereas mutations in Notch and Wnt pathways significantly prolonged survival in MPA. Besides, we demonstrated that mutations in immune-related genes influenced outcomes, with mutations in TP53, Ataxia Telangiectasia Mutated (ATM), Polymerase (DNA) Delta 1 (POLD1), and Epidermal Growth Factor Receptor (EGFR) correlated with worsened survival.ConclusionsWe not only depicted the genetic and immunologic landscape of Chinese MPA but also reveal its distinction from LUAD in genomic and immune context. Our findings may provide opportunities for therapeutic susceptibility among Chinese MPA patients.
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Project description:Craniomandibular osteopathy (CMO) and calvarial hyperostotic syndrome (CHS) are proliferative, non-neoplastic disorders affecting the skull bones in young dogs. Different forms of these hyperostotic disorders have been described in many dog breeds. However, an incompletely dominant causative variant for CMO affecting splicing of SLC37A2 has been reported so far only in three Terrier breeds. The purpose of this study was to identify further possible causative genetic variants associated with CHS in an American Staffordshire Terrier, as well as CMO in seven affected dogs of different breeds. We investigated their whole-genome sequences (WGS) and filtered variants using 584 unrelated genomes, which revealed no variants shared across all affected dogs. However, filtering for private variants of each case separately yielded plausible dominantly inherited candidate variants in three of the eight cases. In an Australian Terrier, a heterozygous missense variant in the COL1A1 gene (c.1786G>A; p.(Val596Ile)) was discovered. A pathogenic missense variant in COL1A1 was previously reported in humans with infantile cortical hyperostosis, or Caffey disease, resembling canine CMO. Furthermore, in a Basset Hound, a heterozygous most likely pathogenic splice site variant was found in SLC37A2 (c.1446+1G>A), predicted to lead to exon skipping as shown before in SLC37A2-associated canine CMO of Terriers. Lastly, in a Weimaraner, a heterozygous frameshift variant in SLC35D1 (c.1021_1024delTCAG; p.(Ser341ArgfsTer22)) might cause CMO due to the critical role of SLC35D1 in chondrogenesis and skeletal development. Our study indicates allelic and locus heterogeneity for canine CMO and illustrates the current possibilities and limitations of WGS-based precision medicine in dogs.
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Project description:The polysaccharide capsule is a major virulence factor of Streptococcus pneumoniae and the target of all currently licensed pneumococcal vaccines. At present, there are 92 serologically distinct pneumococcal serotypes. Structural and antigenic variation of capsular types is the result of genetic variation within the capsular polysaccharide synthesis (CPS) locus; however, genetic variation may not always result in phenotypic differences which produce novel serotypes. With the introduction of high throughput whole genome sequencing, discovery of novel genotypic variants is not unexpected and this study describes a novel variant of the serotype 23B CPS operon. This novel variant was characterized as a novel genotypic subtype (23B1) with ∼70% homology to the published 23B CPS sequence. High sequence variability was determined in eight cps genes involved in sugar biosynthesis. However, there was no distinction between the classic 23B serotype and 23B1 serologically or in terms of polysaccharide structure. Phylogenetic and eBURST analysis revealed a distinct lineage for 23B1 with multiple clones (UK, Thailand, and USA) that arose at different points during pneumococcal evolution. Analysis of the UK S. pneumoniae isolates (n = 121) revealed an upsurge of 23B1 ST2372 in 2011, after which this previously unseen ST increased to reach 50% proportion of the 23B sequenced isolates from 2013 and remained prevalent within our sequenced isolates from later years. Therefore, although the 23B1 variant appears to have no phenotypic impact and cannot be considered as novel serotype, it appears to have led to a genetic restructuring of the UK serotype 23B population.
| S-EPMC5581491 | biostudies-literature
Project description:Esophageal adenocarcinoma (EAC) is highly mutated and molecularly heterogeneous. The number of cell lines available for study is limited and their genome has been only partially characterized. The availability of an accurate annotation of their mutational landscape is crucial for accurate experimental design and correct interpretation of genotype-phenotype findings. We performed high coverage, paired end whole genome sequencing on eight EAC cell lines-ESO26, ESO51, FLO-1, JH-EsoAd1, OACM5.1 C, OACP4 C, OE33, SK-GT-4-all verified against original patient material, and one esophageal high grade dysplasia cell line, CP-D. We have made available the aligned sequence data and report single nucleotide variants (SNVs), small insertions and deletions (indels), and copy number alterations, identified by comparison with the human reference genome and known single nucleotide polymorphisms (SNPs). We compare these putative mutations to mutations found in primary tissue EAC samples, to inform the use of these cell lines as a model of EAC.
| S-EPMC4991527 | biostudies-literature
Project description:BackgroundThe prognosis of mucinous adenocarcinoma (MAC) and non-mucinous adenocarcinoma (NMAC) in colorectal cancer (CRC) is controversial, and the molecular differences between them are unclear.MethodsBetween 2000 and 2010, a total of 1,483 CRC patients were included. Among them, 73 patients (4.9%) were diagnosed with MAC. The clinicopathological features and genetic alterations were compared between MAC and NMAC.ResultsAfter propensity score matching to balance age and sex between MAC and NMAC patients, 292 CRC patients (73 MAC and 219 NMAC) were enrolled in the analysis at a 1:3 ratio. In right-sided colon cancer, patients with MAC were more likely to have Borrmann types 3 and 4 tumors, poor differentiation, and advanced T category and tumor, node, metastasis (TNM) stage, chemotherapy, and a similar 5-year overall survival (OS) rate compared with patients with NMAC. In left-sided colon cancer and rectal cancer, patients with MAC were more likely to have Borrmann types 3 and 4 tumors, poor differentiation, lymphovascular invasion, advanced T and N categories and TNM stages, chemotherapy, and a worse 5-year OS rate than patients with NMAC. Regarding genetic alterations, for NMAC, right-sided colon cancer had more BRAF mutations than left-sided colon cancer and rectal cancer. For MAC, right-sided colon cancer was associated with more microsatellite instability-high tumors and more AKT1 mutations than left-sided colon cancer and rectal cancer.ConclusionThe genetic alterations are distinct between MAC and NMAC in CRC. Tumor location may have an impact on genetic alterations and patient prognosis in MAC and NMAC.
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Project description:Tumors rich in stroma are associated with advanced stage and poor prognosis in colorectal adenocarcinoma (CRC). Abundance of stromal cells also has implications for genomic analysis of patient tumors as it may prevent detection of somatic mutations. As part of our efforts to interrogate stroma-cancer cell interactions and to identify actionable therapeutic targets in metastatic CRC, we aimed to determine the proportion of stroma embedded in hepatic CRC metastases by performing computational tumor purity analysis based on whole exome sequencing data (WES). Unlike previous studies focusing on histopathologically prescreened samples, we used an unbiased in-house collection of tumor specimens. WES from CRC liver metastasis samples were utilized to evaluate stromal content and to assess the performance of three in silico tumor purity tools, ABSOLUTE, Sequenza and PureCN. Matching tumor derived organoids were analyzed as a high purity control as they are enriched in cancer cells. Computational purity estimates were compared to those from a histopathological assessment conducted by a board-certified pathologist. According to all computational methods, metastatic specimens had a median tumor purity of 30% whereas the organoids were enriched for cancer cells with a median purity estimate of 94%. In line with this, variant allele frequencies (VAFs) of oncogenes and tumor suppressor genes were undetectable or low in most patient tumors, but higher in matching organoid cultures. Positive correlation was observed between VAFs and in silico tumor purity estimates. Sequenza and PureCN produced concordant results whereas ABSOLUTE yielded lower purity estimates for all samples. Our data shows that unbiased sample selection combined with molecular, computational, and histopathological tumor purity assessment is critical to determine the level of stroma embedded in metastatic colorectal adenocarcinoma.
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Project description:The present study reports a rare case of synchronous colorectal mucinous adenocarcinoma (CMAC) and pancreatic ductal adenocarcinoma (PDAC). A 61-year-old man complained of hematochezia for half a month. Colonoscopy and biopsy in a local hospital revealed mucinous adenocarcinoma in the sigmoid colon, and a subsequent abdominal computed tomography examination in Ren Ji Hospital (Shanghai, China) identified an unexpectedly hypovascular lesion in the body and tail of the pancreas, in addition to a mass in the colon. The patient then underwent combined surgery consisting of a distal pancreaticosplenectomy and a sigmoidectomy, and the postoperative pathological tests confirmed the co-occurrence of CMAC and PDAC. Next-generation sequencing demonstrated no deleterious germline mutations, but did find some critical somatic mutations concerning both tumors. The patient received 12 cycles of a combination of 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (modified FOLFIRINOX regimen) as adjuvant chemotherapy thereafter. Complete remission was achieved at 1 year after the surgery. To the best of our knowledge, this is the first documented case of such synchronous malignances (CMAC and PDAC) in the literature, and its publication therefore improves our overall understanding in this field.
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