SATB1 (MIM #602075) is a relatively new gene reported only in recent years in association with neurodevelopmental disorders characterized by variable facial dysmorphisms, global developmental delay, poor or absent speech, altered electroencephalogram (EEG), and brain abnormalities on imaging. To date about thirty variants in forty-four patients/children have been described, with a heterogeneous spectrum of clinical manifestations. In the present study, we describe a new patient affected by mild intellectual disability, speech disorder, and non-specific abnormalities on EEG and neuroimaging. Family studies identified a new de novo frameshift variant c.1818delG (p.(Gln606Hisfs*101)) in SATB1. To better define genotype-phenotype associations in the different types of reported SATB1 variants, we reviewed clinical data from our patient and from the literature and compared manifestations (epileptic activity, EEG abnormalities and abnormal brain imaging) due to missense variants versus those attributable to loss-of-function/premature termination variants. Our analyses showed that the latter variants are associated with less severe, non-specific clinical features when compared with the more severe phenotypes due to missense variants. These findings provide new insights into SATB1-related disorders.

SATB2-associated syndrome (SAS) is a rare condition, and it is characterized by severe developmental delay/intellectual disability, especially severe speech delay/or absence, craniofacial abnormalities, and behavioral problems. Most of the published reports are limited to children, with little information about the natural history of the disease and the possible novel signs and symptoms or behavioral changes in adulthood. We describe the management and follow-up of a 25-year-old male with SAS due to a de novo heterozygous nonsense variant SATB2:c.715C>T:p.(Arg239*) identified by whole-exome sequencing and review the literature. The case herein described contributes to a better characterization of the natural history of this genetic condition and in addition to the genotype-phenotype correlation of the SATB2:c.715C>T:p.(Arg239*) variant in SAS, highlights some particularities of its management.

Small nucleolar RNA host gene 8 (SNHG8) is a long non-coding RNA that has physiological roles in epithelial and muscle satellite cells. This lncRNA has been reported to be over-expressed in a variety of cancer cell lines. Its silencing has attenuated tumor growth in animal models of cancers. SNHG8 can be served as a molecular sponge for some miRNAs to regulate their target genes. miR-634/ZBTB20, miR-335-5p/PYGO2, miR588/ATG7, miR-152/c-MET, miR-1270/BACH1, miR-491/PDGFRA, miR-512-5p/TRIM28, miR-149-5p/PPM1F, miR-542-3p/CCND1/CDK6, miR-656-3p/SERBP1, miR-656-3p/SATB1, miR-1270/S100A11 and miR-384/HOXB7 are examples of molecular axes being regulated by SNHG8 in the context of cancer. Moreover, it can affect pathogenesis of atherosclerosis, chronic cerebral ischemia, acute gouty arthritis, ischemic stroke and myocardial infarction through modulation of a number of molecular axes such as SNHG8/miR-384/Hoxa13/FAM3A and miR-335/RASA1 as well as NF-κB signaling pathway. The current review aims at summarization of the role of SNHG8 in diverse human disorders.

SATB2-associated syndrome (SAS; OMIM: 612,313) is an autosomal dominant inherited multisystemic disorder caused by several variants of the SATB2 gene. SAS is characterized by intellectual disability, developmental delay, severe speech anomalies, craniofacial anomalies, and dental abnormalities. Here, we report the dental phenotype of primary dentition of three Chinese children with SAS.
All three cases with SAS showed intellectual disability, speech and language anomalies, and palate anomalies. For the dental phenotype, all three cases showed macrodontia, crowded dentition, extensive caries, periapical abscesses and fistulas. Radiographs showed the wide-open root apex of deciduous teeth, loss of mandibular second bicuspids, delayed root formation of permanent teeth, rotated teeth, and taurodontism. Sanger sequencing of case 1 showed that there was a heterozygous code shift variation, c1985delT (p.F662Sfs*9) in the SATB2 gene, which has not been reported in literature. Root canal therapy, carious restoration, and teeth extraction were managed promptly, while preventive dental care was given regularly.
The dental phenotype of primary dentition in SAS may show macrodontia, crowded dentition, severe caries, wide-open root apex of deciduous teeth, loss of mandibular second bicuspids, delayed root formation of permanent teeth, rotated teeth, and taurodontism. Regular oral hygiene instructions and preventive dental care are both required.

SATB2-associated syndrome (SAS) is a rare disorder characterized by developmental delay, behavioral problems, and craniofacial anomalies in particular dental and palatal abnormalities. We describe the clinical course, genetic and autopsy findings in a Chinese boy with global developmental delay, hypotonia, epilepsy, recurrent fractures and osteopenia. Brain magnetic resonance imaging showed pachygyria, white matter hypoplasia and hypogenesis of the corpus callosum. Whole-exome sequencing identified a novel heterozygous missense variant c.1555G>A p.(Glu519Lys) in the SATB2 gene. Unfortunately, he died at 26 months of bronchiolitis and pneumonia. Autopsy revealed pachygyria which was more severe anteriorly, dilated lateral and third ventricles and partial agenesis of the corpus callosum. Histology showed features compatible with two-layered lissencephaly. The bone showed disordered lamination and bone matrix. Although SATB2 has been shown to be involved in the regulation of neuronal migration in the developing brain, lissencephaly has not been reported so far. This could represent a more severe phenotype of SAS.

Globally, 15-20% of all children diagnosed with leukemia suffer from acute myeloid leukemia (AML), a rapidly progressive, clinically and biologically heterogeneous disease leading to the impaired differentiation of myeloid blast cells. Although 80% of patients achieve complete remission after induction chemotherapy, many relapse, negatively affecting overall out comes. The mechanisms underlying relapse have not been fully elucidated. This review aims to provide an overview of genetic aberrations involved in relapse of disease. A literature review on molecular mechanisms implicated in pediatric AML relapse spanning from 2003 to 2017 was conducted. PubMed, Medline, and Google Scholar were interrogated using relevant search terms. Of note, we examined a total of final 10 research papers from four large study groups that have utilized whole genome sequencing and molecular targeting of trio or paired samples of initial diagnosis, remission, and relapse. Their findings reveal that the genomic landscape of pediatric AML varies from diagnosis to relapse in different populations. Pediatric AML relapse is a systemic evolutionary illness accompanied by synchronized mutational hits impairing differentiation function. The irregular proliferative function is a consequence of mutations in signal transduction genes such as FLT3, RAS, PTPN11, and c-KIT and genes that code for transcription factors such as CEBPα, WT1, SATB1, GFI1, KLF2, and TBP are associated with relapse of disease. Identification of molecular markers unique to different stages of the disease in distinct populations can provide valuable information about disease prognosis and management.

Intestinal-type adenocarcinoma of the primary salivary glands is extremely rare. So far, only 11 cases of primary intestinal-type adenocarcinoma of the oral cavity and major salivary glands have been reported. Two of those tumors arose in the floor of mouth, 7 in the tongue, and 2 in the major salivary glands. However, it has remained unclear whether these tumors are derived from mature salivary glands, and primary intestinal-type adenocarcinoma of the buccal mucosa has not been reported previously. Here, we present the first documented case of primary intestinal-type adenocarcinoma arising in a minor salivary gland of the buccal mucosa. Histopathologically, the tumor resembled a well-differentiated or mucinous colonic adenocarcinoma. Immunohistochemically, the tumor cells were diffusely positive for AE1/AE3, CAM5.2, CK7, SATB2, β-catenin, p53, Ki-67, MUC2, and MUC5 AC. CK14 and CK20 were positive in some of the tumor cells. CDX2, CA19-9, SP-A, TTF-1, PSA, SMA, p63, and cyclin D1 were negative in the tumor cells. The tumor in the present case may have originated from salivary gland duct epithelium that underwent transformation to phenotypic intestinal-type epithelium. In this very rare case of primary intestinal-type adenocarcinoma of the buccal mucosa, we considered diagnostic markers that could be indicative of mature salivary gland origin.

BACKGROUND: To study the clinical and genetic features from a Chinese child with SATB2-associated syndrome (SAS) and review of literature.
METHODS: The girl, 2 years 3 months old, is admitted to the Department of Pediatric Rehabilitation in our hospital. This patient has mental retardation, language development disorder, cleft palate II0, micrognathia, malocclusion, irritability and bilateral oblique palpebral fissure as a clinical manifestation and is treated for 3 months.
RESULTS: Gesell Development Scale (GDS) evaluation displays the patient\'s action capacity: gross motor 13.4, DQ 41%; fine motor 14.1, DQ 44%; adaptive behavior: DA 15.2, DQ 47%; speech capacity: DA 8.8; DQ 27%; person capacity: DA 11.7, DQ, 36%. Bayley Scale evaluation displays MDI < 50 and PDI < 50. Sleep EEG showed bilateral frontal pole - frontal - central - anterior temporal area presents in sharp wave, sharp and slow wave synchronization issue. A brain MRI showed that signal T2 is strengthened in the internal capsule hind leg. Flake T2FLATR high signal can been showed in the periventricular area of the parietal lobe in bilateral hemisphere. Molecular studies showed the patient carries a de novo nonsense mutation c.1285G>A (p.R429X) in SATB2.
CONCLUSIONS: SATB2 mutation is not detected in the parents of the subjects. This study is important to further study the clinical features of SATB2-associated syndrome and to enlarge the SATB2 mutation spectrum.

SATB2 is part of the family of matrix attachment region-binding transcription factors, and has developmental roles in craniofacial, neural, and osteoblastic differentiation. Recently, SATB2 has been shown to be highly expressed in the epithelium of the lower gastrointestinal tract, with a relatively narrow expression profile in malignancies, including colorectal/appendiceal adenocarcinomas, tumors of osteoblastic differentiation, and renal/urothelial carcinomas. SATB2 has gained interest as a relatively specific marker of colorectal differentiation, with potential applications including determining origin of adenocarcinomas of unknown primary and distinguishing primary ovarian mucinous adenocarcinomas from colorectal metastases. Here, we briefly review the biology, expression profile, and potential histologic applications of SATB2.

BACKGROUND: The special AT-rich sequence-binding proteins 1 (SATB1) is a major regulator involved in cell differentiation. It has been shown that SATB1 acts as an oncogenic regulator. The clinical and prognostic significance of SATB1 in gastrointestinal cancer remains controversial. The purpose of this study is to conduct a systematic review and meta-analysis to elucidate the impact of SATB1 in gastrointestinal cancer.
RESULTS: A total of 3174 gastrointestinal cancer patients from 15 studies were included. The correlation between SATB1 expression and OS or RFS was investigated in 12 and 5 studies respectively. The results of meta-analysis showed that SATB1 overexpression is inversely correlated with OS (combined HR: 1.79, p = 0.0003) and RFS (combined HR: 2.46, p < 0.0001). In subgroup analysis, SATB1 expression is significantly correlated with poor prognosis in gastrointestinal cancer in Asian population. SATB1 expression is associated with stage, invasion depth, lymph node metastasis and distant metastasis.
METHODS: Published studies with data on overall survival (OS) and/or relapse free survival (RFS) and SATB1 expression were searched from Cochrane Library, PubMed and Embase (up to Dec 30, 2016). The outcome measurement is hazard ratio (HR) for OS or RFS related with SATB1 expression. Two reviewers independently screened the literatures, extracted the data and performed meta-analysis using RevMan 5.3.0 software. The combined HRs were calculated by fixed- or random-effect models.
CONCLUSIONS: The results of this meta-analysis suggest that SATB1 overexpression is related to advanced stage, lymph node metastasis and distant metastasis. SATB1 overexpression is a marker indicating poor prognosis in gastrointestinal cancer.