Genomic and Genic Deletions of the FOX Gene Cluster on 16q24.1 and Inactivating Mutations of FOXF1 Cause Alveolar Capillary Dysplasia and Other Malformations

Stankiewicz, Paweł; Pei, Sen; Bhatt, Samarth; Storer, Mekayla; Xia, Zhilian; Bejjani, Bassem A.; Ou, Zhishuo; Wiszniewska, Joanna; Driscoll, Daniel J.; Maisenbacher, Melissa; Bolívar, Juan M.; Bauer, Mislen; Zackai, Elaine H.; McDonald‐McGinn, Donna M.; Nowaczyk, Malgorzata M.J.; Murray, Mitzi L.; Hustead, Virginia A.; Mascotti, Kristin; Schultz, Regina; Hallam, Lavinia; McRae, D. Harold; Nicholson, Andrew G.; Newbury, Robert; Durham-O'Donnell, Jane; Knight, G. R.; Kini, Usha; Shaikh, Tamim H.; Martin, Vicki; Tyreman, Matthew; Simonic, Ingrid; Willatt, Lionel; Paterson, Joan; Mehta, Sarju G.; Jones, Christy W.; Rajan, Diana; Fitzgerald, Tomas; Gribble, Susan; Prigmore, Elena; Patel, Ankita; Shaffer, Lisa G.; Carter, Nigel P.; Cheung, Sau Wai; Langston, Claire; Shaw‐Smith, Charles

doi:10.1016/j.ajhg.2009.08.013

Cited by 60 publications

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“…FENDRR plays an essential role in mammalian embryogenesis (Grote and Herrmann, 2013). Expression of FENDRR has been detected in the lung, and is associated with a lethal lung developmental disorder (Stankiewicz et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Distinct temporal changes in host cell lncRNA expression during the course of an adenovirus infection

et al. 2016

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The deregulation of cellular long non-coding RNA (lncRNA) expression during a human adenovirus infection was studied by deep sequencing. Expression of lncRNAs increased substantially following the progression of the infection. Among 645 significantly expressed lncRNAs, the expression of 398 was changed more than 2-fold. More than 80% of them were up-regulated and 80% of them were detected during the late phase. Based on the genomic locations of the deregulated lncRNAs in relation to known mRNAs and miRNAs, they were predicted to be involved in growth, structure, apoptosis and wound healing in the early phase, cell proliferation in the intermediate phase and protein synthesis, modification and transport in the late phase. The most significant functions of cellular RNA-binding proteins, previously shown to interact with the deregulated lncRNAs identified here, are involved in RNA splicing, nuclear export and translation events. We hypothesize that adenoviruses exploit the lncRNA network to optimize their reproduction.

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Section: Discussionmentioning

confidence: 99%

Distinct temporal changes in host cell lncRNA expression during the course of an adenovirus infection

et al. 2016

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“…Recently, microdeletions encompassing the FOX cluster at 16q24.1 have been reported to result in alveolar capillary dysplasia together with a broad spectrum of additional malformations, including HLHS. The authors speculated that deletions or inactivating mutations involving FOXC2 and FOXL1 may contribute to HLHS (12).…”

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confidence: 99%

Identification of de novo mutations and rare variants in hypoplastic left heart syndrome

et al. 2011

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Hypoplastic left heart syndrome (HLHS) is one of the most severe congenital heart malformations, characterized by underdevelopment of the structures in the left heart-aorta complex. The majority of cases are sporadic. Although multiple genetic loci have been tentatively implicated in HLHS, no gene or pathway seems to be specifically associated with the disease. To elucidate the genetic basis of HLHS, we analyzed 53 well-characterized patients with isolated HLHS using an integrated genomic approach that combined DNA sequencing of five candidate genes (NKX2-5, NOTCH1, HAND1, FOXC2 and FOXL1) and genome-wide screening by high-resolution array comparative genomic hybridization. In 30 patients, we identified two novel de novo mutations in NOTCH1, 23 rare patients inherited gene variants in NOTCH1, FOXC2 and FOXL1, and 33 rare patients mostly inherited copy-number variants. Some of the identified variations coexisted in the same patient. The biological significance of such rare variations is unknown, but our findings strengthen the role of NOTCH pathway in cardiac valve development, indicating that HLHS is, at least in part, a 'valve' disease. This is the first report of de novo mutations associated with isolated HLHS. Moreover, the coexistence of multiple rare variants suggests in some cases a cumulative effect, as shown for other complex disease.

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“…PTC, papillary thyroid cancer epigenetic mechanisms, such as heterozygous point mutations, genomic deletions and methylation. 26,27 In this study, we also examined FOXF1 somatic mutations, gene-level CNAs and the methylation status of 57 CpG sites in more than 350 classical PTC cases. However, we failed to identify any expression-related genetic and epigenetic alterations.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic analysis of the prognostic value and potential regulatory network of FOXF1 in papillary thyroid cancer

2019

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FOXF1 belongs to the forkhead family of transcription factors. In this study, we aimed to explore the expression profile of FOXF1 in papillary thyroid cancer (PTC) and corresponding adjacent normal tissues, by using data from The Cancer Genome Atlas‐Thyroid Cancer (TCGA‐THCA) and The Genotype‐Tissue Expression (GTEx) project. Also, we studied its prognostic significance in PTC and its potential regulatory network. Results showed that FOXF1 expression was significantly lower in PTC tissues compared with adjacent normal tissues. Subgroup analysis only confirmed the downregulation in classical histological variant, but not in tall‐cell and follicular variants. FOXF1 downregulation was associated with advanced T stages, positive nodal invasion, and advanced pathological stages of the classical variants. FOXF1 expression might be a fair prognostic marker in terms of recurrence, which independently predicted favorable RFS (HR:0.114, 95%CI: 0.045–0.289, p < .001). We examined FOXF1 somatic mutations, gene‐level copy number alterations (CNAs) and the methylation status of 57 CpG sites in more than 350 classical PTC cases. However, no expression‐related genetic and epigenetic alterations were identified. Based on 20,048 genes with RNA‐seq data, we identified 16 genes that showed strongly positive co‐expression (Pearson's r ≥ 0.6) with FOXF1. Available evidence showed that some of the genes have well‐characterized tumor suppressive effects. We hypothesized that some of these genes might be the upstream regulators or downstream effectors of FOXF1 in classical PTC. In conclusion, FOXF1 mRNA was typically downregulated in classical PTC. Its expression might be a specific and independent prognostic biomarker in terms of RFS in classical PTC patients.

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Genomic and Genic Deletions of the FOX Gene Cluster on 16q24.1 and Inactivating Mutations of FOXF1 Cause Alveolar Capillary Dysplasia and Other Malformations

Abstract: The American Journal of Human Genetics 85 (2009) 537-537. doi:10.1016/j.ajhg.2009.08.013Received by publisher: 0000-01-01Harvest Date: 2016-01-04 12:18:59DOI: 10.1016/j.ajhg.2009.08.013Page Range: 537-53

Cited by 60 publications

References 0 publications

Distinct temporal changes in host cell lncRNA expression during the course of an adenovirus infection

Distinct temporal changes in host cell lncRNA expression during the course of an adenovirus infection

Identification of de novo mutations and rare variants in hypoplastic left heart syndrome

Bioinformatic analysis of the prognostic value and potential regulatory network of FOXF1 in papillary thyroid cancer

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