• DNA mutations
• dental diseases
• environmental risk factors
• genetic contribution
• inheritance pattern
• oral conditions

• R21 CA267006 NCI NIH HHS
• 1C06TW267006-23A21 NIH HHS

• CUT domain
• Msx1 promoter
• SATB2
• SATB2‐associated syndrome
• cleft palate
• homeobox domain
• tooth agenesis

• JPMJSP2120 Japan Science and Technology Agency (JST SPRING)
• 19K10376 Japan Society for the Promotion of Science
• 22K10239 Japan Society for the Promotion of Science
• JP24ek0109760 Initiative on Rare and Undiagnosed Diseases of the Japan Agency for Medical Research and Development

• Genetic mutations
• Genetic syndrome
• Head and neck tumors
• Misdiagnosis
• Odontogenic tumors

• chromatin
• congenital birth defects
• craniofacial
• epigenetics
• neural crest

• Humans
• Epigenesis, Genetic/genetics
• Cleft Palate/genetics
• Cleft Palate/metabolism
• Neural Crest/metabolism
• Signal Transduction/genetics
• Cleft Lip/genetics
• Cleft Lip/metabolism

• K99 DE031349 NIDCR NIH HHS
• R01 DE024034 NIDCR NIH HHS
• R01 DE030377 NIDCR NIH HHS
• K99/R00 DE031349 NIDCR NIH HHS

• SATB2 gene
• SATB2-associated syndrome
• de novo mutation
• glass syndrome
• hereditary disease

• SATB2-associated syndrome
• craniofacial defect
• tooth anomaly

• Japan Agency for Medical Research and Development

and importance: Complex odontomas are hamartomas representing a conglomeration of all dental tissues. When developed, they rarely become giant and even more rare to become giant in children. This report presented an unusual giant mandibular complex odontoma in very young patient. It also provided a literature analysis and better understanding of clinical features of such giant lesions in the mandible.

An 8-year-old boy presented with swelling in the right side of the mandible. After clinical and radiological exams, a provisional diagnosis of giant composite odontoma was made. This lesion led to jaw expansion, asymmetrical face, and teeth eruption alterations. Surgical excision of the lesion was performed, and histopathological examination confirmed the diagnosis. The patient's follow-up showed that normal jaw size and facial symmetry was restored with no evidence of recurrence for 3 years.

A literature review of reported mandibular large odontomas was made. All published reported cases of giant odontoma in the mandible caused bone expansion with or without pain. According to the literature, this paper described the youngest patient with giant complex odontoma in the mandible. This was also the first reported case from Syria.

Giant complex composite odontoma of the mandible can develop at any age causing facial asymmetry, however, with good prognosis and predictable surgical treatment.

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This report presented an unusual giant mandibular complex odontoma in a young patient.

Special AT-rich sequence binding protein 2 (SATB2)-associated syndrome (SAS; OMIM 612313) is an autosomal dominant disorder. Alterations in the SATB2 gene have been identified as causative.

We report a case of a 13-year-old Chinese boy with lifelong global developmental delay, speech and language delay, and intellectual disabilities. He had short stature and irregular dentition, but no other abnormal clinical findings. A de novo heterozygous nonsense point mutation was detected by genetic analysis in exon 6 of SATB2, c.687C>A (p.Y229X) (NCBI reference sequence: NM_001172509.2), and neither of his parents had the mutation. This mutation is the first reported and was evaluated as pathogenic according to the guidelines from the American College of Medical Genetics and Genomics. SAS was diagnosed, and special education performed. Our report of a SAS case in China caused by a SATB2 mutation expanded the genotype options for the disease. The heterogeneous manifestations can be induced by complicated pathogenic involvements and functions of SATB2 from reviewed literatures: (1) SATB2 haploinsufficiency; (2) the interference of truncated SATB2 protein to wild-type SATB2; and (3) different numerous genes regulated by SATB2 in brain and skeletal development in different developmental stages.

Global developmental delays are usually the initial presentations, and the diagnosis was challenging before other presentations occurred. Regular follow-up and genetic analysis can help to diagnose SAS early. Verification for genes affected by SATB2 mutations for heterogeneous manifestations may help to clarify the possible pathogenesis of SAS in the future.

• Special AT-rich sequence binding protein 2
• SATB2-associated syndrome
• Global developmental delay
• Developmental speech and language delay
• Case report

• Bmp9
• Satb2
• bone
• mesenchymal stem cells
• odontogenic differentiation
• osteo
• tooth

• Adenoviridae/genetics
• Animals
• Bone Regeneration
• Cell Adhesion
• Cell Differentiation
• Cell Line
• Cell Proliferation
• Cell Self Renewal
• Genetic Vectors/genetics
• Genetic Vectors/metabolism
• Growth Differentiation Factor 2/genetics
• Growth Differentiation Factor 2/metabolism
• Hydrogels/chemistry
• Incisor/cytology
• Matrix Attachment Region Binding Proteins/antagonists & inhibitors
• Matrix Attachment Region Binding Proteins/genetics
• Matrix Attachment Region Binding Proteins/metabolism
• Mesenchymal Stem Cells/cytology
• Mesenchymal Stem Cells/metabolism
• Mice
• Mice, Inbred C57BL
• Odontoblasts/cytology
• Odontoblasts/metabolism
• RNA Interference
• RNA, Small Interfering/metabolism
• Tissue Scaffolds/chemistry
• Transcription Factors/antagonists & inhibitors
• Transcription Factors/genetics
• Transcription Factors/metabolism

• 81870758 National Natural Science Foundation of China
• KJQN201800436 Scientific and Technological Research Program of Chongqing Municipal Education Commission
• National Natural Science Foundation of China
• Scientific and Technological Research Program of Chongqing Municipal Education Commission

Recent genomic and scRNA-seq analyses of melanoma demonstrated a lack of recurrent genetic drivers of metastasis, while identifying common transcriptional states correlating with invasion or drug resistance. To test whether transcriptional adaptation can drive melanoma progression, we made use of a zebrafish mitfa:BRAFV600E;tp53-/- model, in which malignant progression is characterized by minimal genetic evolution. We undertook an overexpression-screen of 80 epigenetic/transcriptional regulators and found neural crest-mesenchyme developmental regulator SATB2 to accelerate aggressive melanoma development. Its overexpression induces invadopodia formation and invasion in zebrafish tumors and human melanoma cell lines. SATB2 binds and activates neural crest-regulators, including pdgfab and snai2. The transcriptional program induced by SATB2 overlaps with known MITF^lowAXL^high and AQP1⁺NGFR1^high drug-resistant states and functionally drives enhanced tumor propagation and resistance to Vemurafenib in vivo. In summary, we show that melanoma transcriptional rewiring by SATB2 to a neural crest mesenchyme-like program can drive invasion and drug resistance in autochthonous tumors.

• SATB2
• cancer biology
• drug resistance
• epigenetics
• melanoma
• metastasis
• neural crest
• zebrafish

SATB2 (special AT-rich sequence-binding protein 2) is a member of the special AT-rich binding protein family. As a transcription regulator, SATB2 mainly integrates higher-order chromatin organization. SATB2 expression appears to be tissue- and stage-specific, and is governed by several cellular signaling molecules and mediators. Expressed in branchial arches and osteoblast-lineage cells, SATB2 plays a significant role in craniofacial pattern and skeleton development. In addition to regulating osteogenic differentiation, SATB2 also displays versatile functions in neural development and cancer progression. As an osteoinductive factor, SATB2 holds great promise in improving bone regeneration toward bone defect repair. In this review, we have summarized our current understanding of the physiological and pathological functions of SATB2 in craniofacial and skeleton development, neurogenesis, tumorigenesis and regenerative medicine.

• Bone regeneration
• Development
• Neurogenesis
• SATB2
• Tumorigenesis