Gastrointestinal stromal tumors (GISTs) are the mesenchymal tumors of the gastrointestinal tract. Extra Gastrointestinal stromal tumors (EGISTs) are rare neoplasms that occur outside the gastrointestinal tract [1]. Miettinen et al. [2] described the first EGIST in 1999. EGIST accounts for 10% of all GISTs [3]. The main distinction between GIST and EGIST is the site of origin of the primary tumor, as GIST occurs throughout the GI tract, from the esophagus to the anus, whereas EGIST is a tumor without any connection with the intestinal wall and are reported in the retroperitoneum, mesentery, and omentum [4]. Hu et al. [5] reported a first case report of EGIST of larynx.We present a second case report of Extra-gastrointestinal stromal tumor of larynx a 47-year-old male reported to ENT Department Command Hospital Central Command Lucknow with complaints of Hoarseness. On examination found to have right vocal cord growth for which he underwent excision of right vocal cord growth. Histopathological examination showed typical of a spindle-cell GIST, showing strong immunoreactivity for CD 117, DOG1, Vimentin and CD 99. 6 months follow up post surgery with no recurrence.

As sessile organisms, plants enter periods of dormancy in response to environmental stresses to ensure continued growth and reproduction in future. During dormancy, plant growth is suppressed, adaptive/survival mechanisms are exerted, and stress tolerance increases over a prolonged period until the plants resume their development or reproduction under favorable conditions. In this review, we focus on seed dormancy and bud dormancy, which are critical for adaptations to fluctuating environmental conditions. We provide an overview of the physiological characteristics of both types of dormancy as well as the importance of the phytohormones abscissic acid and gibberellin for establishing and releasing dormancy, respectively. Additionally, recent epigenetic analyses have revealed that dormancy establishment and release are associated with the removal and deposition of histone modifications at the loci of key regulatory genes influencing phytohormone metabolism and signaling, including DELAY OF GERMINATION 1 and DORMANCY-ASSOCIATED MADS-box genes. We discuss our current understanding of the physiological and molecular mechanisms required to establish and release seed dormancy and bud dormancy, while also describing how environmental conditions control dormancy depth, with a focus on the effects of histone modifications.

Seed dormancy governs germination timing, with both evolutionary and applied consequences. Despite extensive studies on the hormonal and genetic control of these processes, molecular mechanisms directly linking dormancy and germination remain poorly understood. By screening a collection of lines overexpressing Arabidopsis transcription factors, we identified ERF50 as a key gene to control dormancy and germination. To study its regulation, we measured seed-related physiological parameters in loss-of-function mutants and carried out transactivation, protein interaction and ChIP-PCR analyses. We found direct ERF50-mediated repression of DOG1 and activation of EXPA2 transcription, which results in enhanced seed germination. Although ERF50 expression is increased by DOG1 in dormant seeds, ERF50 germination-promoting activity is blocked by RGL2. The physiological, genetic and molecular evidence gathered here supports that ERF50 controls germination timing by regulating DOG1 levels to leverage its role as enhancer of seed germination, via RGL2 antagonism on EXPA2 expression. Our results highlight the central role of ERF50 as a feedback regulator to couple and fine-tune seed dormancy and germination.

High temperatures can significantly impact wheat growth and grain yields during the grain-filling stage. In this study, we identified genes that respond to high-temperature stress during the grain-filling stage. We also identified and characterized 24 novel genes of the DOG1 gene family in hexaploid wheat. Motif analysis and conserved domain search revealed substantial similarities among TaDOG1 family members. Phylogenetic analysis demonstrated the evolutionary conservation of the TaDOG1 family across various plant species. Tissue-specific expression profiling indicated consistent patterns, with TaDOG1 genes predominantly expressed in stem tissues. Only TaDOG1-1 exhibited enhanced expression, particularly during hard dough and ripening stages. TaDOG1-1 and TaDOG1-7 exhibited increased expression under heat stress during the grain-filling stage, indicating their heat-responsive nature. Cis-element analysis revealed potential regulatory motifs, suggesting the involvement of TaDOG1-1 and TaDOG1-7 in stress tolerance mechanisms. Yeast two-hybrid screening revealed interacting proteins, including stress-responsive and grain development-associated proteins. To understand the biological function, we overexpressed TaDOG1-1 in Arabidopsis plants and observed enhanced thermotolerance under basal heat stress. Under heat stress, the transgenic plants exhibited increased biomass and elevated expression levels of heat-responsive genes. Furthermore, TaDOG1-1-overexpressing plants showed improved survival rates under soil heat stress, along with a greater accumulation of antioxidant enzymes in leaves. In this study, the identification and functions of the DOG1 gene family provide valuable insights for developing genetic engineering strategies aimed at improving wheat yield under high-temperature stress.

Aquaporins (AQPs) regulate the transport of water and other substrates, aiding plants in adapting to stressful environments. However, the knowledge of AQPs in salt-secreting and viviparous Avicennia marina is limited. In this study, 46 AmAQPs were identified in A. marina genome, and their subcellular localisation and function in transporting H2 O2 and boron were assessed through bioinformatics analysis and yeast transformation. Through analysing their expression patterns via RNAseq and real-time quantitative polymerase chain reaction, we found that most AmAQPs were downregulated in response to salt and tidal flooding. AmPIP (1;1, 1;7, 2;8, 2;9) and AmTIP (1;5, 1;6) as salt-tolerant candidate genes may contribute to salt secretion together with Na+ /H+ antiporters. AmPIP2;1 and AmTIP1;5 were upregulated during tidal flooding and may be regulated by anaerobic-responsive element and ethylene-responsive element cis-elements, aiding in adaptation to tidal inundation. Additionally, we found that the loss of the seed desiccation and dormancy-related TIP3 gene, and the loss of the seed dormancy regulator DOG1 gene, or DOG1 protein lack heme-binding capacity, may be genetic factors contributing to vivipary. Our findings shed light on the role of AQPs in A. marina adaptation to intertidal environments and their relevance to salt secretion and vivipary.

DELAY OF GERMINATION 1 is a key regulator of dormancy in flowering plants before seed germination. Bryophytes develop haploid spores with an analogous function to seeds. Here, we investigate whether DOG1 function during germination is conserved between bryophytes and flowering plants and analyse the underlying mechanism of DOG1 action in the moss Physcomitrium patens. Phylogenetic and in silico expression analyses were performed to identify and characterise DOG1 domain-containing genes in P. patens. Germination assays were performed to characterise a Ppdog1-like1 mutant, and replacement with AtDOG1 was carried out. Yeast two-hybrid assays were used to test the interaction of the PpDOG1-like protein with DELLA proteins from P. patens and A. thaliana. P. patens possesses nine DOG1 domain-containing genes. The DOG1-like protein PpDOG1-L1 (Pp3c3_9650) interacts with PpDELLAa and PpDELLAb and the A. thaliana DELLA protein AtRGA in yeast. Protein truncations revealed the DOG1 domain as necessary and sufficient for interaction with PpDELLA proteins. Spores of Ppdog1-l1 mutant germinate faster than wild type, but replacement with AtDOG1 reverses this effect. Our data demonstrate a role for the PpDOG1-LIKE1 protein in moss spore germination, possibly alongside PpDELLAs. This suggests a conserved DOG1 domain function in germination, albeit with differential adaptation of regulatory networks in seed and spore germination.

Production of morphologically and physiologically variable seeds is an important strategy that helps plants to survive in unpredictable natural conditions. However, the model plant Arabidopsis thaliana and most agronomically essential crops produce visually homogenous seeds. Using automated phenotype analysis, we observed that small seeds in Arabidopsis tend to have higher primary and secondary dormancy levels than large seeds. Transcriptomic analysis revealed distinct gene expression profiles between large and small seeds. Large seeds have higher expression of translation-related genes implicated in germination competence. By contrast, small seeds have elevated expression of many positive regulators of dormancy, including a key regulator of this process, the DOG1 gene. Differences in DOG1 expression are associated with differential production of its alternative cleavage and polyadenylation isoforms; in small seeds, the proximal poly(A) site is selected, resulting in a short mRNA isoform. Furthermore, single-seed RNA sequencing analysis demonstrated that large seeds resemble DOG1 knockout mutant seeds. Finally, on the single-seed level, expression of genes affected by seed size is correlated with expression of genes that position seeds on the path toward germination. Our results demonstrate an unexpected link between seed size and dormancy phenotypes in a species that produces highly homogenous seed pools, suggesting that the correlation between seed morphology and physiology is more widespread than initially assumed.

UNASSIGNED: Determining the risk of malignant behaviour and mutational status of gastrointestinal stromal tumours (GISTs) guide the management decision and allow optimal individualized patient treatment.
UNASSIGNED: To determine clinicopathological, immunohistochemical (IHC), risk and KIT mutational findings of GISTs in Sudanese patients.
UNASSIGNED: Histological slides were reviewed, IHC for DOG-1 and CD117 performed and hotspot KIT mutations examined. The risk group was assigned using combined risk criteria.
UNASSIGNED: 21 of the 36 patients (58.3%) were males (mean age, 54.83 ±12.57; range, 26-71). Abdominal pain and mass were the most frequent symptoms. Mean tumor size (±SD) was 11.6(±5.82) cm. Either CD117, DOG1 or both were positive in all cases. Using risk criteria, 33.3% (n=12) were clinically malignant at presentation, 13.9% (n=5) high risk, 16.7% (n=6) intermediate, 27.8% (n=10) low risk and 2.8% (n=1) very low risk. Sixteen of 23 (70%) tested cases had KIT (14 exon 11 and two exon 9) mutations. Six tumors were wild type. Exon 11 deletions (p.I563-L576 del and p.V559-N566delinsD) significantly correlate with disease recurrence (p-value: 0.028).
UNASSIGNED: Sudanese patients with GIST tend to present late. Nearly half of them correspond to the malignant/high-risk category. The frequency of KIT mutations (79.31%) is in line with the literature.

Despite its characteristic clinicopathological features, chondroblastoma may pose a diagnostic challenge, given its morphological spectrum, potential for subdiagnostic appearances in limited biopsy specimens, and its potential mimicry of other entities. Recently, a characteristic H3F3B mutation underlying most chondroblastomas was described, which led to the identification of H3.3K36M as the corresponding diagnostic immunohistochemical marker. The present study is an evaluation of immunohistochemical features of 26 chondroblastomas, including DOG1 and H3.3K36M immunostaining. H3.3K36M immunostaining was graded as 1+, 2+ and 3+ in terms of staining intensity. There were 17 males and 9 females (M:F = 1.8:1) with ages ranging from 7 to 34 years (average = 16.7, median = 16). The most common location was proximal humerus (8, 30.7 %) followed by proximal tibia (5, 19.2 %), distal femur (3, 11.5 %), proximal femur (3, 11.5 %), pelvis (2,), followed by distal tibia, calcaneum, upper sternum, scapula, and D9 vertebra, in a single case, respectively. Eighteen (69.23 %) tumors displayed all the classic histopathological features. Immunohistochemically, the tumor cells were positive for S-100 P (19/22, 86.3 %), DOG1 (focal to patchy) (21/23 91.3 %), and H3.3K36M (26/26, 100 %). H3.3K36M tested in other tumors, constituting diagnostic mimics of a chondroblastoma, such as giant cell tumor of bone, chondromyxoid fibroma, and tenosynovial giant cell tumors, showed negative staining. Six tumors, initially diagnosed as chondroblastomas were reclassified into other entities with the help of negative H3.3K36M immunostaining. The present study reinforces H3.3K36M as a highly sensitive and specific marker for diagnosing chondroblastoma, including small biopsies, and in uncommon tumor sites with variable histopathological features. DOG1 is also useful in reinforcing a diagnosis of chondroblastoma in a clinicoradiological context, especially in laboratories lacking H3.3K36M immunostain. However, its staining pattern is variable.

Neuroendocrine neoplasms represent a heterogeneous group of rare tumors, more frequently arising from gastroenteropancreatic tract and lungs. At the time of diagnosis, 20% of cases are metastatic, and 10% of cases are considered as cancer of unknown primary origin. Several immunohistochemical markers are routinely used to confirm the neuroendocrine differentiation, first among all Synaptophysin and Chromogranin-A; on the other hand, different immunohistochemical markers are used to establish primary anatomical site, as TTF1, CDX2, Islet-1 and Calcitonin, but no marker is available in order to distinguish among different sites of the digestive tract. DOG1 (discovered on GIST-1) is a gene normally expressed in interstitial cells of Cajal and, in routine practice, DOG1 immunostaining is used in diagnosis of GIST (gastrointestinal stromal tumor). DOG1 expression has been described in several neoplasms other than GIST, both in mesenchymal and epithelial neoplasms. In the present study, DOG1 immunostaining has been performed in a large cohort of neuroendocrine neoplasms, including neuroendocrine tumors and neuroendocrine carcinomas, in order to evaluate frequency, intensity and pattern of expression in different anatomical site and in different tumor grade. DOG1 expression was detected in a large percentage of neuroendocrine tumors, with statistically significant association between DOG1 expression and gastrointestinal tract neuroendocrine tumors. As a consequence, DOG1 could be included in marker panel for the identification of primary site in neuroendocrine metastases of unknown primary origin; moreover, these results recommend careful evaluation of DOG1 expression in gastrointestinal neoplasms, in particular in differential diagnosis between epithelioid GIST and neuroendocrine tumors.