ARID1A

OBJECTIVE: Ovarian clear cell carcinomas (OCCCs) constitute a rare ovarian cancer subtype with distinct clinical features, but may nonetheless be difficult to distinguish morphologically from other subtypes. There is limited knowledge of genetic events driving OCCC tumorigenesis beyond ARID1A, which is reportedly mutated in 30-50% of OCCCs. We aimed to further characterize OCCCs by combined global transcriptional profiling and targeted deep sequencing of a panel of well-established cancer genes...

Innate lymphoid cells (ILCs) communicate with other haematopoietic and non-haematopoietic cells to regulate immunity, inflammation and tissue homeostasis. How these ILC lineages develop and are maintained is not clear. Here we show that WASH is highly expressed in the nucleus of group 3 ILCs (ILC3s). WASH deletion impairs the cell pool of NKp46(+) ILC3s. In NKp46(+) ILC3s, WASH recruits Arid1a to the Ahr promoter thus activating AHR expression. WASH deletion in ILC3s decreases the number of NKp46(+) ILC3s. Moreover, Arid1a deletion impedes AHR expression and impairs the maintenance of NKp46(+) ILC3s...

BACKGROUND: Molecular characterization of nonmuscle invasive bladder cancer (NMIBC) may provide a biologic rationale for treatment response and novel therapeutic strategies. OBJECTIVE: To identify genetic alterations with potential clinical implications in NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Pretreatment index tumors and matched germline DNA from 105 patients with NMIBC on a prospective Institutional Review Board-approved protocol underwent targeted exon sequencing analysis in a Clinical Laboratory Improvement Amendments-certified clinical laboratory...

PURPOSE: Preparing for precision medicine, we surveyed genomic alterations in esophageal squamous cell carcinoma (ESCC) and identified candidate therapeutic targets by genomic profiling using next-generation sequencing (NGS). MATERIALS AND METHODS: Single-nucleotide variations, indels, and copy number variations in 80 genes were evaluated by targeted deep sequencing in 24 surgically resected ESCC specimens. Immunohistochemistry analyses and silver in situ hybridization for ERBB2 (HER2) were conducted to verify the NGS results...

Invasive micropapillary carcinoma (IMPC) of the breast is a highly aggressive and a rare subtype of breast cancer. In this study, we aimed to investigate differences between pure and mixed IMPCs of the breast in terms of clinicopathologic features, and also to analyze the significance of expressions of ARID1A and bcl-2 regarding prognosis. Sixty-nine of IMPCs consisting of 21 pure and 48 mixed type diagnosed at Pathology Department of Istanbul Medical Faculty between 2000 and 2011, who had complete follow-up data, were collected to analyze ARID1A and bcl-2 expressions immunohistochemically with prognosis...

Primary hepatocellular carcinoma (HCC) mainly develops in subjects chronically infected with hepatitis B (HBV) and C (HCV) viruses through a multistep process characterized by the accumulation of genetic alterations in the human genome. Nucleotide changes in coding regions (i.e. TP53, CTNNB1, ARID1A and ARID2) as well as in non-coding regions (i.e. TERT promoter) are considered cancer drivers for HCC development with variable frequencies in different geographic regions depending on the etiology and environmental factors...

BACKGROUND: Long-standing ulcerative colitis (UC) leading to colorectal cancer (CRC) is one of the most serious and life-threatening consequences acknowledged globally. Ulcerative colitis-associated colorectal carcinogenesis showed distinct molecular alterations when compared with sporadic colorectal carcinoma. METHODS: Targeted sequencing of 409 genes in tissue samples of 18 long-standing UC subjects at high risk of colorectal carcinoma (UCHR) was performed to identify somatic driver mutations, which may be involved in the molecular changes during the transformation of non-dysplastic mucosa to high-grade dysplasia...

BACKGROUND & AIMS: Early-onset gastric cancer, which develops in younger patients than most gastric cancers, is usually detected at advanced stages, has diffuse histologic features, and occurs more frequently in women. We investigated somatic genomic alterations associated with the unique characteristics of sporadic diffuse gastric cancers (DGCs) from younger patients. METHODS: We conducted whole exome and RNA sequence analyses of 80 resected DGC samples from patients 45 years old or younger in Korea...

POLE exonuclease domain mutations have recently been described in undifferentiated endometrial carcinoma but, because of the rarity of this aggressive type of endometrial cancer, their prognostic significance is unknown. We have analyzed the immunophenotype (ARID1A, MLH1, PMS2, MSH2, MSH6, p53, β-catenin, and SMARCB1) and mutational status (POLE, PIK3CA, and PTEN) of 21 undifferentiated carcinomas (8 undifferentiated and 13 dedifferentiated carcinomas). Loss of ARID1A expression was observed in 9 of 19 cases (47%), loss of expression of at least 1 DNA mismatch repair protein in 7 (7/21; 33%), and p53 immunoreaction was aberrant (mutated/inactivated) in 11 cases (11/21; 52%)...

BACKGROUND: Endometriosis, defined as the presence of ectopic endometrial stroma and epithelium, affects approximately 10% of reproductive-age women and can cause pelvic pain and infertility. Endometriotic lesions are considered to be benign inflammatory lesions but have cancerlike features such as local invasion and resistance to apoptosis. METHODS: We analyzed deeply infiltrating endometriotic lesions from 27 patients by means of exomewide sequencing (24 patients) or cancer-driver targeted sequencing (3 patients)...

BACKGROUND: The molecular pathogenesis of clear cell endometrial cancer (CCEC), a tumor type with a relatively unfavorable prognosis, is not well defined. We searched exome-wide for novel somatically mutated genes in CCEC and assessed the mutational spectrum of known and candidate driver genes in a large cohort of cases. METHODS: We conducted whole exome sequencing of paired tumor-normal DNAs from 16 cases of CCEC (12 CCECs and the CCEC components of 4 mixed histology tumors)...

The chromatin remodeler AT-Rich Interactive Domain 1A (ARID1A) is frequently mutated in ovarian clear cell carcinoma (OCCC) and endometriosis precursor lesions. Here, we show that knocking down ARID1A in an immortalized endometriosis cell line is sufficient to induce phenotypic changes indicative of neoplastic transformation as evidenced by higher efficiency of anchorage-independent growth, increased propensity to adhere to collagen, and greater capacity to invade basement membrane extract in vitro. ARID1A knockdown is associated with expression dysregulation of 99 target genes, and many of these expression changes are also observed in primary OCCC tissues...

Oxidative stress is considered an important factor in the development of endometriosis, including its malignant transformation. Previous studies have found that AT-rich interactive domain 1A (ARID1A), a tumor suppressor gene, is frequently mutated and inactivated in endometriosis-associated ovarian cancer (EAOC), and such a change in this gene is considered an early event in malignant transformation. We observed oxidative stress status by measuring the activity of the antioxidant enzyme manganese superoxide dismutase (MnSOD), malondialdehyde (MDA), and ARID1A gene expression in tissue samples from patients with endometriosis, EAOC, or non-endometriosis-associated ovarian cancer (non-EAOC)...

The tumor suppressor gene, AT Rich Interactive Domain 1A (ARID1A) mutation has been reported in a variety of cancers, especially the endometrium-related gynecological cancers, including the ovarian clear cell carcinoma, ovarian endometrioid carcinoma and uterine endometrioid carcinoma. However, the prognostic value of ARID1A in endometrium-related gynecological cancers is still inconclusive. Therefore, we performed this meta-analysis to evaluate the clinical significance of ARID1A in endometrium-related gynecological cancers...

OBJECTIVE: Limited data have been obtained in regard to pulmonary metastasis (PM) in patients with stage I endometrial cancer. The aims of the study were (1) to present the clinical and pathological characteristics of patients with PM in the setting of stage I endometrioid-type endometrial cancer (EEC) and (2) to define possible factors that may be used to predict PM. METHODS: Six hundred thirty patients with stage I EEC, including 12 with PM, 19 with extra-PM (EPM), and 599 with no recurrence, were observed...

Intratumoral heterogeneity (ITH) is a prominent feature of kidney cancer. It is not known whether it has utility in finding associations between protein expression and clinical parameters. We used ITH that is detected by immunohistochemistry (IHC) to aid the association analysis between the loss of SWI/SNF components and clinical parameters.160 ccRCC tumors (40 per tumor stage) were used to generate tissue microarray (TMA). Four foci from different regions of each tumor were selected. IHC was performed against PBRM1, ARID1A, SETD2, SMARCA4, and SMARCA2...

CONTEXT: - The clinicopathologic and prognostic significance of ARID1A mutation in esophageal adenocarcinoma (EAC) is unknown. OBJECTIVE: - To determine the morphological correlates and prognostic significance of ARID1A-deficient EAC. DESIGN: - One hundred twenty cases of primary EAC were evaluated for a predetermined set of histologic features and immunohistochemistry for ARID1A, p53, and MLH1 performed on EAC, as well as adjacent Barrett esophagus and Barrett esophagus-associated dysplasia, when feasible...

Gene transcription is a central tenet of biology, traditionally measured by RT-PCR, microarray, or more recently, RNA sequencing. However, these measurements only provide a snapshot of the state of gene transcription and only represent an overall readout of complex transcriptional networks that regulate gene expression. In this report, we describe a novel strategy to dissect endogenous gene transcription regulation in live cells by knocking in a reporter gene, EGFP, under the control of the endogenous gene promoter, using the ARID1A gene as an example...

Background: Although the role of epigenetic abnormalities has been studied for several years in cancer genesis and development, epigenetic-targeting drugs have historically failed to demonstrate efficacy in solid malignancies. However, successful targeting of chromatin remodeling deficiencies, histone writers and histone reader alterations has been achieved very recently using biomarker-driven and mechanism-based approaches. Epigenetic targeting is now one of the most active areas in drug development and could represent novel therapeutic opportunity for up to 25% of all solid tumors...

BACKGROUND: Next-generation sequencing (NGS) with a multi-gene panel is now available for patients with lung adenocarcinoma, but the performance characteristics and clinical utility of this testing are not well-described. We present the results of an extended 467 gene panel in a series of advanced, highly selected nonsmall cell lung cancer (NSCLC) patients using a range of specimens, including predominantly small biopsy and cytology specimens. MATERIALS AND METHODS: A retrospective review of 22 NSCLC biopsies sent for NGS using an extended gene panel from January 2014 to July 2015...