With the improvement of high-throughput genomic technology such as microarray and next-generation sequencing over the last ten to twenty year, we have come to know that the portion of the genome responsible for protein coding constitutes just approximately 1.5%. The remaining 98.5% of the genome not responsible for protein coding have been regarded as 'junk DNA'. More recently, however, 'Encyclopedia of DNA elements project' revealed that most of the junk DNA were transcribed to RNA regardless of being translated into proteins. In addition, many reports support that a lot of these non-coding RNAs play a role in gene regulation. In fact, there are various functioning short non-coding RNAs including rRNA, tRNA, small interfering RNA, and micro RNA. Mechanisms of these RNAs are relatively well-known. Until recently, however, little is known about long non-coding RNAs which consist of 200 nucleotides or more. In this article, we will review the representative long non-coding RNAs which have been reported to be related to gastrointestinal cancers and to play a certain role in its pathogenesis.
Gastrointestinal Neoplasms/*genetics/*metabolism/pathology ; Humans ; Liver Neoplasms/genetics/metabolism/pathology ; RNA, Long Noncoding/genetics/*metabolism

With the improvement of high-throughput genomic technology such as microarray and next-generation sequencing over the last ten to twenty year, we have come to know that the portion of the genome responsible for protein coding constitutes just approximately 1.5%. The remaining 98.5% of the genome not responsible for protein coding have been regarded as 'junk DNA'. More recently, however, 'Encyclopedia of DNA elements project' revealed that most of the junk DNA were transcribed to RNA regardless of being translated into proteins. In addition, many reports support that a lot of these non-coding RNAs play a role in gene regulation. In fact, there are various functioning short non-coding RNAs including rRNA, tRNA, small interfering RNA, and micro RNA. Mechanisms of these RNAs are relatively well-known. Until recently, however, little is known about long non-coding RNAs which consist of 200 nucleotides or more. In this article, we will review the representative long non-coding RNAs which have been reported to be related to gastrointestinal cancers and to play a certain role in its pathogenesis.
Gastrointestinal Neoplasms/*genetics/*metabolism/pathology ; Humans ; Liver Neoplasms/genetics/metabolism/pathology ; RNA, Long Noncoding/genetics/*metabolism

Cell Differentiation ; Cytodiagnosis ; Gastrointestinal Neoplasms ; genetics ; immunology ; pathology ; Humans ; Immunophenotyping ; Stromal Cells ; pathology

Familial juvenile polyposis (FJP) is a rare autosomal dominant hereditary disorder that is characterized by the development of multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of cancer. Recently, germline mutations, including mutations in the SMAD4, BMPR1A, PTEN and, possibly, ENG genes, have been found in patients with juvenile polyps. We herein report a family with juvenile polyposis syndrome (JPS) with a novel germline mutation in the SMAD4 gene. A 21-year-old man presented with rectal bleeding and was found to have multiple polyps in his stomach, small bowel, and colon. His mother had a history of gastrectomy for multiple gastric polyps with anemia and a history of colectomy for colon cancer. A review of the histology of the polyps revealed juvenile polyps in both patients. Subsequently, mutation screening in DNA samples from the patients revealed a germline mutation in the SMAD4 gene. The pair had a novel mutation in exon 10 (stop codon at tyrosine 413). To our knowledge, this mutation has not been previously described. Careful family history collection and genetic screening in JPS patients are needed to identify FJP, and regular surveillance is recommended.
Exons ; Female ; Gastrointestinal Neoplasms/*genetics/pathology ; Germ-Line Mutation ; Humans ; Intestinal Polyposis/*congenital/genetics/pathology ; Male ; Middle Aged ; Neoplastic Syndromes, Hereditary/*genetics/pathology ; Smad4 Protein/*genetics ; Young Adult

To analyze the association of Epstein-Barr virus (EBV) with gastrointestinal non-Hodgkin's lymphomas arising in immunocompetent patients, 56 consecutive cases of gastrointestinal lymphomas (B-cell: 52-cases, T-cell: 3 cases, T/NK-cell: 1 case) occurring in the stomach (33 cases), intestine (22 cases) and esophagus (1 case) were investigated for the presence of EBV using polymerase chain reaction analysis as a screening method followed by EBER-1 RNA and DNA in situ hybridization (ISH) and immunohistochemistry for the expression of latent membrane protein 1 (LMP-1). Forty-seven cases demonstrated extractable DNA and EBV DNA was detected only in 4 cases. Among the, RNA (EBER-1) and DNA ISH analysis confirmed the presence of the EBV genome in tumor cells in 3 cases (T/NK-cell lymphoma of ileum, gastric high-grade B-cell lymphoma of mucosa-associated lymphoid tissue, gastric diffuse large B-cell lymphoma). Only the T/NK cell lymphoma showed diffuse positivity of tumor cells while 2 gastric B-cell lymphomas demonstrated a scattered positive reaction and no cases expressed LMP-1. Nine cases without extractable DNA by the PCR method showed no nuclear signal by EBER-1 ISH. These findings suggest that most sporadic primary gastrointestinal lymphomas in Korea are not associated with EBV.
Gastrointestinal Neoplasms/virology* ; Gastrointestinal Neoplasms/pathology ; Genome, Viral ; Herpesvirus 4, Human/isolation & purification* ; Herpesvirus 4, Human/genetics ; Human ; In Situ Hybridization ; Korea ; Lymphoma/virology* ; Lymphoma/pathology ; Polymerase Chain Reaction

Humans ; Sarcoma, Small Cell/pathology* ; Transcription Factors ; Gastrointestinal Tract/pathology* ; Oncogene Proteins, Fusion/genetics* ; Biomarkers, Tumor ; Soft Tissue Neoplasms

Gastrointestinal stromal tumors (GISTs) of the gallbladder are representative of an extremely rare group of tumors. We have encountered a patient with a malignant GIST of the gallbladder and presented it with a review of some articles. A 72-yr-old woman initially presented with right upper quadrant abdominal pain, fever and chills. Emergency cholecystectomy was performed under the impression of gallbladder empyema. Liver metastasis was found at 7 months postoperatively and the patient expired 9 months after the surgery. At the time of cholecystectomy, the gallbladder showed a necrotic serosal surface with an irregular thickened wall. A mass, 6 cm in length and 3 cm in width, encircled the whole wall of the neck and upper body of the gallbladder. Microscopic findings revealed frequent mitotic figures (more than 20/50 HPF) and tumor necrosis. Hyperchromatic, pleomorphic and spindle shaped neoplastic cells that were arranged in a pattern of short fascicles infiltrated the entire layer of the gallbladder. The tumor cells were immunoreactive for CD117 antigen (c-kit protein) and vimentin. They were negative for desmin, smooth muscle actin and S-100 protein. Mutations of the c-kit proto-oncogene were not found in this case. These findings were sufficient to provide enough clinical, histopathological and immunohistochemicalevidence in diagnosing our case as a malignant GIST.
Aged ; Female ; Gallbladder Neoplasms/genetics/metabolism/*pathology ; Gastrointestinal Stromal Tumors/genetics/metabolism/*pathology ; Humans ; Proto-Oncogene Protein c-kit/genetics/metabolism

OBJECTIVEGastrointestinal stromal tumors (GISTs) have a broad spectrum of biological behaviors ranging from benign, borderline and malignant. This study aimed to screen differentially expressed microRNAs (miRNAs) between malignant and borderline GISTs and to investigate the potential role of miRNAs in the malignant transformation of GISTs.

METHODSSix GIST samples including borderline tumors (n = 3) and malignant tumors (n = 3) were collected based on the clinical and pathological characteristics. Total RNA was extracted, followed by miRNA microarray analysis to screen the differentially expressed miRNAs. The most significantly expressed 4 miRNAs were then chosen for further validation by real-time PCR in 22 additional GIST samples.

RESULTSDirect comparison of malignant group versus borderline group revealed 14 significantly and differentially expressed miRNAs (P < 0.05, with a fold change of < 0.5 or > 2). Five miRNAs were up-regulated and nine were down-regulated in the malignant group. Four miRNAs (miR-221, miR-135b, miR-675(*) and miR-218) were most significantly and differentially expressed between the two groups. The differential expression of 2 miRNAs (miR-221 and miR-675(*)) were subsequently confirmed with good concordance by real-time PCR.

CONCLUSIONSThe differential miRNA expression profiles between two groups are revealed by miRNA microarray assay, and confirmed by real-time PCR. Among differentially expressed miRNAs, miR-221 and miR-675(*) might be related to the malignant transformation of GISTs, and have a potential value in predicting biological behavior of GISTs.

Adult ; Aged ; Aged, 80 and over ; Cell Transformation, Neoplastic ; Down-Regulation ; Female ; Gastrointestinal Neoplasms ; genetics ; pathology ; Gastrointestinal Stromal Tumors ; genetics ; pathology ; Gene Expression Profiling ; Humans ; Male ; MicroRNAs ; genetics ; metabolism ; Microarray Analysis ; Middle Aged ; Real-Time Polymerase Chain Reaction ; Up-Regulation

Pain perception is influenced by multiple factors. The single nucleotide polymorphisms (SNPs) of some genes were found associated with pain perception. This study aimed to examine the association of the genotypes of ABCB1 C3435T, OPRM1 A118G and COMT V108/158M (valine 108/158 methionine) with pain perception in cancer patients. We genotyped 146 cancer pain patients and 139 cancer patients without pain for ABCB1 C3435T (rs1045642), OPRM1 A118G (rs1799971) and COMT V108/158M (rs4680) by the fluorescent dye-terminator cycle sequencing method, and compared the genotype distribution between groups with different pain intensities by chi-square test and pain scores between groups with different genotypes by non-parametric test. The results showed that in these cancer patients, the frequency of variant T allele of ABCB1 C3435T was 40.5%; that of G allele of OPRM1 A118G was 38.5% and that of A allele of COMT V108/158M was 23.3%. No significant difference in the genotype distribution of ABCB1 C3435T (rs1045642) and OPRM1 A118G (rs1799971) was observed between cancer pain group and control group (P=0.364 and 0.578); however, significant difference occurred in the genotype distribution of COMT V108/158M (rs4680) between the two groups (P=0.001). And the difference could not be explained by any other confounding factors. Moreover, we found that the genotypes of COMT V108/158M and ABCB1 C3435T were associated with the intensities of pain in cancer patients. In conclusion, our results indicate that the SNPs of COMT V108/158M and ABCB1 C3435T significantly influence the pain perception in Chinese cancer patients.
ATP Binding Cassette Transporter, Sub-Family B ; genetics ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Breast Neoplasms ; complications ; diagnosis ; genetics ; pathology ; Catechol O-Methyltransferase ; genetics ; Female ; Gastrointestinal Neoplasms ; complications ; diagnosis ; genetics ; pathology ; Gene Expression ; Gene Frequency ; Genital Neoplasms, Female ; complications ; diagnosis ; genetics ; pathology ; Genital Neoplasms, Male ; complications ; diagnosis ; genetics ; pathology ; Genotype ; Humans ; Lung Neoplasms ; complications ; diagnosis ; genetics ; pathology ; Male ; Middle Aged ; Pain ; complications ; diagnosis ; genetics ; pathology ; Pain Measurement ; Pain Perception ; Polymorphism, Single Nucleotide ; Receptors, Opioid, mu ; genetics

Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; therapeutic use ; Cadherins ; genetics ; metabolism ; Carcinoma, Papillary ; pathology ; Cetuximab ; Colorectal Neoplasms ; drug therapy ; genetics ; pathology ; Consensus ; Dissent and Disputes ; Drug Delivery Systems ; Epithelial-Mesenchymal Transition ; Gastrointestinal Neoplasms ; classification ; pathology ; Genes, ras ; Humans ; Mutation ; Neoplasm Invasiveness ; Neoplastic Syndromes, Hereditary ; genetics ; metabolism ; pathology ; Neuroendocrine Tumors ; classification ; pathology ; Precancerous Conditions ; pathology ; Stomach Neoplasms ; genetics ; metabolism ; pathology