1.The KIT Exon 11 Stop Codon Mutation in Gastrointestinal Stromal Tumors: What Is the Clinical Meaning?.
Angela MICHELUCCI ; Caterina CHIAPPETTA ; Jessica CACCIOTTI ; Norman VECCIA ; Elisa ASTRI ; Martina LEOPIZZI ; Romana PROSPERI PORTA ; Vincenzo PETROZZA ; Carlo DELLA ROCCA ; Generoso BEVILACQUA ; Andrea CAVAZZANA ; Claudio DI CRISTOFANO
Gut and Liver 2013;7(1):35-40
BACKGROUND/AIMS: Gastrointestinal stromal tumors (GISTs) strongly express a receptor tyrosine kinase (RTK, c-KIT-CD117) harboring a KIT mutation that causes constitutive receptor activation leading to the development and growth of tumors; 35% of GISTs without KIT mutations have platelet-derived growth factor receptor alpha (PDGFRA) mutations, and the type of mutation plays an important role in the response to treatment. This study aimed to establish the frequency of stop codon mutations in the RTKs, KIT, and PDGFRA, in GISTs and correlate this molecular alteration with protein expression and treatment responsiveness. METHODS: Seventy-nine GISTs were analyzed for both KIT and PDGFRA mutations. Immunohistochemical expression was studied in tissue microarray blocks. RESULTS: We found three rare KIT mutations in exon 11 that induced a stop codon, two at position 563 and one at position 589, which have never been described before. All three tumors were CD117-, DOG1-, and CD34-positive. Two patients with a KIT stop codon mutation did not respond to imatinib therapy and died shortly after treatment. CONCLUSIONS: The association between stop codon mutations in KIT and patient survival, if confirmed in a larger population, may be useful in choosing effective therapies.
Benzamides
;
Codon, Terminator
;
Exons
;
Gastrointestinal Stromal Tumors
;
Growth and Development
;
Humans
;
Piperazines
;
Protein-Tyrosine Kinases
;
Pyrimidines
;
Receptor, Platelet-Derived Growth Factor alpha
;
Receptors, Platelet-Derived Growth Factor
2.A Case of Myeloid Neoplasm with a PDGFRB Rearrangement and Eosinophilia.
Nam Gil CHO ; Daejin KIM ; Minjung SHIM ; So Young CHONG
Korean Journal of Medicine 2017;92(1):79-83
Myeloid neoplasia with eosinophilia and platelet-derived growth factor receptor beta (PDGFRB) rearrangements is an uncommon Philadelphia-negative myeloproliferative neoplasm. Their most common morphological diagnosis is chronic myelomonocytic leukemia with eosinophilia, which is associated with t(5;12)(q33;p13) and results in the formation of the ETV6-PDGFRB fusion gene. Here, we report a 49-year-old man with a myeloid neoplasm with a PDGFRB rearrangement, who was incidentally diagnosed with hyperleukocytosis and eosinophilia during a health screening. A chromosome analysis of a bone marrow sample revealed 46, XY, t(5;12)(q33;p13), and fluorescence in situ hybridization analysis revealed the PDGFRB gene rearrangement. The patient was treated with imatinib and subsequently achieved complete hematological and molecular remission.
Bone Marrow
;
Diagnosis
;
Eosinophilia*
;
Fluorescence
;
Gene Rearrangement
;
Humans
;
Imatinib Mesylate
;
In Situ Hybridization
;
Leukemia, Myelomonocytic, Chronic
;
Mass Screening
;
Middle Aged
;
Myeloproliferative Disorders
;
Receptor, Platelet-Derived Growth Factor beta*
;
Receptors, Platelet-Derived Growth Factor
3.A case of myeloid neoplasm with the PDGFRB rearrangement and eosinophilia.
Sang Eon JANG ; Hye Jin KANG ; Yoon Hwan CHANG ; Dong Soon LEE ; Hyeon Tae KIM ; Kyung Won KOH ; Sung Hyun YANG
Korean Journal of Medicine 2010;78(3):386-390
Myeloid neoplasm with the platelet-derived growth factor receptor beta (PDGFRB) rearrangement is a myeloproliferative neoplasm. Patients with this disease often have prominent eosinophilia or monocytosis and the presence of t(5;12)(q31~33;p12) or a variant translocation with expression of an ETV6-PDGFRB fusion gene or the PDGFRB rearrangement. We report an 82-year-old woman with a myeloid neoplasm, with the PDGFRB rearrangement, who presented with a dry cough, eosinophilia and thrombocytosis. The chromosome study of the bone marrow showed 46,XX,ins(1;5)(q22;q33q13.3), and fluorescence in situ hybridization (FISH) analysis revealed rearrangement of the PDGFRB gene. The patient was successfully treated with low-dose imatinib.
Aged, 80 and over
;
Benzamides
;
Bone Marrow
;
Cough
;
Eosinophilia
;
Female
;
Fluorescence
;
Humans
;
In Situ Hybridization
;
Piperazines
;
Pyrimidines
;
Receptor, Platelet-Derived Growth Factor beta
;
Receptors, Platelet-Derived Growth Factor
;
Thrombocytosis
;
Imatinib Mesylate
4.The Significance of Interstitial Cells in Neurogastroenterology.
Peter J BLAIR ; Poong Lyul RHEE ; Kenton M SANDERS ; Sean M WARD
Journal of Neurogastroenterology and Motility 2014;20(3):294-317
Smooth muscle layers of the gastrointestinal tract consist of a heterogeneous population of cells that include enteric neurons, several classes of interstitial cells of mesenchymal origin, a variety of immune cells and smooth muscle cells (SMCs). Over the last number of years the complexity of the interactions between these cell types has begun to emerge. For example, interstitial cells, consisting of both interstitial cells of Cajal (ICC) and platelet-derived growth factor receptor alpha-positive (PDGFRalpha+) cells generate pacemaker activity throughout the gastrointestinal (GI) tract and also transduce enteric motor nerve signals and mechanosensitivity to adjacent SMCs. ICC and PDGFRalpha+ cells are electrically coupled to SMCs possibly via gap junctions forming a multicellular functional syncytium termed the SIP syncytium. Cells that make up the SIP syncytium are highly specialized containing unique receptors, ion channels and intracellular signaling pathways that regulate the excitability of GI muscles. The unique role of these cells in coordinating GI motility is evident by the altered motility patterns in animal models where interstitial cell networks are disrupted. Although considerable advances have been made in recent years on our understanding of the roles of these cells within the SIP syncytium, the full physiological functions of these cells and the consequences of their disruption in GI muscles have not been clearly defined. This review gives a synopsis of the history of interstitial cell discovery and highlights recent advances in structural, molecular expression and functional roles of these cells in the GI tract.
Enteric Nervous System
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Gap Junctions
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Gastrointestinal Tract
;
Giant Cells
;
Interstitial Cells of Cajal
;
Ion Channels
;
Models, Animal
;
Muscle, Smooth
;
Muscles
;
Myocytes, Smooth Muscle
;
Neurons
;
Receptor, Platelet-Derived Growth Factor alpha
;
Receptors, Platelet-Derived Growth Factor
5.Relationship of overexpression of angiogenesis factors and their receptors with invasive growth of keloid.
Du-yin JIANG ; Xiao-bing FU ; Wei CHEN ; Tong-zhu SUN
Chinese Journal of Plastic Surgery 2004;20(2):128-131
OBJECTIVETo study the relationship between invasive growth and the angiogenesis factors and their receptors in keloid.
METHODSBiopsies from 17 keloid (Ke) were divided into atrophy group (Ke-A, n = 9), proliferating group (Ke-P, n = 13), infiltrating group (Ke-I, n = 9), normal skin around Ke (Ke-N, n = 10) and normal skin (NS, n = 10). The histology, immunohistochemistry and computerized imaging analysis were used for the study. The levels of basic fibroblast growth factor (bFGF) and its receptor-Flg, vascular endothelial growth factor (VEGF) and VEGF/KDR complex (11B5), and platelet derived growth factor (PDGF-A) and its receptor-PDGFR-alpha, and alpha-smooth muscle actin (alpha-SMA) were determined in specimens with immuneohistochemical staining.
RESULTSIn all 5 groups, bFGF, Flg, VEGF, 11B5, PDGF-A, and PDGFR-alpha were all expressed in fibroblasts (Fb), monocyte-phagocytes, vascular endothelial cells, adventitial cells, epidermal (cells and epithelial cells in appendage. The intensities of staining ranked as follows: Ke-I > Ke-N approximately equal to Ke-P > Ke-A approximately equal to NS, Flg > hFGF approximately equal to PDGFR-alpha > PDGF-A approximately equal to 11B5 > VEGF (P < 0.05 to approximately 0.01). 11B5 and VEGF were expressed (intensively in alpha-SMA positive myofibroblasts only in Ke-I group. The histological observation showed hyperplasia of endothelial cells and obliteration of microvessels.
CONCLUSIONThe invasive growth of keloid may be related to the overexpression of angiogenesis factors and their receptors. The abnormal expression of 11B5 in myofibroblasts may be one of the important factors associated with tumor-like growth feature in the invasive parts sites of keloid. The results suggest that inhibition of these biological activities would be of significance in clinical therapy.
Adolescent ; Adult ; Aged ; Angiogenesis Inducing Agents ; analysis ; Child ; Child, Preschool ; Female ; Fibroblast Growth Factors ; analysis ; Fibroblasts ; chemistry ; pathology ; Humans ; Immunohistochemistry ; Infant ; Keloid ; metabolism ; pathology ; Male ; Middle Aged ; Platelet-Derived Growth Factor ; analysis ; Receptor Protein-Tyrosine Kinases ; analysis ; Receptor, Fibroblast Growth Factor, Type 1 ; Receptor, Platelet-Derived Growth Factor alpha ; analysis ; Receptors, Fibroblast Growth Factor ; analysis ; Receptors, Growth Factor ; analysis ; Skin ; chemistry ; pathology ; Vascular Endothelial Growth Factor A ; analysis
6.Targeted sequencing analysis of hyper-eosinophilic syndrome and chronic eosinophilic leukemia.
Shi Qiang QU ; Tie Jun QIN ; Ze Feng XU ; Yue ZHANG ; Yu Jiao JIA ; Xiao Fei AI ; Hong Li ZHANG ; Li Wei FANG ; Nai Bo HU ; Li Juan PAN ; Bing LI ; Jin Qin LIU ; Kun RU ; Zhi Jian XIAO
Chinese Journal of Hematology 2018;39(6):501-506
Objective: Analysis of the molecular characteristics of eosinophilia. Methods: Targeting sequence to 24 patients with chronic eosinophilic leukemia (CEL) with rearrangement of PDGFRA, PDGFRB, or FGFR1 and 62 patients with hyper-eosinophilic syndrome (HES). Mutation annotation and analysis of amino acid mutation using authoritative databases to speculate on possible pathogenic mutation. Results: Thirty-seven kinds of clonal variant were detected from 17 patients with CEL, no recurrent mutation site and hot spot region were found. No pathogenic mutation was detected in 19 patients with PDGFRA rearrangement, but pathogenic mutations of ASXL1, RUNX1 and NRAS were detected from 2 patients with FGFR1 rearrangement who progressed to acute myeloid leukemia and 1 patient with PDGFRB rearrangement who progressed to T lymphoblastic lymphoma, respectively. One hundred and two kinds of clonal abnormalities were detected in 49 patients with HES. The main hot spot mutation regions included: CEBPA Exon1, TET2 Exon3, ASXL1 Exon12, IDH1 Y208C, and FGFR3 L164V. CRRLF2 P224L and PDGFRB R370C point mutations were detected separately in 2 patients with HES who treated with imatinib monotherapy and achieved hematologic remission. Conclusion: The pathogenesis of CEL with PDGFRA, PDGFRB or FGFR1 rearrangement is usually single, and the progression of the disease may involve other driver mutation. A variety of genes with hot mutation regions may be involved in the pathogenesis of HES, and some mutation sites are sensitive to tyrosine kinase inhibitors.
Chronic Disease
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Humans
;
Hypereosinophilic Syndrome
;
Imatinib Mesylate
;
Leukemia
;
Receptor, Platelet-Derived Growth Factor alpha
;
Receptor, Platelet-Derived Growth Factor beta
7.The Physiologic Roles of the Subepithelial Platelet-derived Growth Factor Receptor alpha-positive Cells in the Colon (Am J Physiol Gastrointest Liver Physiol 2013;304:G823-G834).
Journal of Neurogastroenterology and Motility 2014;20(1):127-128
No abstract available.
Colon*
;
Liver*
;
Platelet-Derived Growth Factor*
;
Receptors, Platelet-Derived Growth Factor*
8.The Expressions of PDGF-C, PDGF-D and PDGF Receptors in Renal Development Model.
Sang Ok MOON ; Eui Sic CHO ; Bang Joo LA ; Kyung Pyo KANG ; Sik LEE ; Mi Jeong SUNG ; Sung Kyew KANG ; Sung Kwang PARK ; Won KIM
Korean Journal of Nephrology 2005;24(2):170-180
BACKGROUND: Four platelet derived growth factor (PDGF) family members have been identified; the classical PDGFs, PDGF-A and PDGF-B, and the novel PDGFs, PDGF-C and PDGF-D, which were only recently discovered. METHODS: The present study was designed to determine the changes of the platelet derived growth factor (PDGF) subtypes (C & D) and their receptors (PDGFR)-alpha & beta expression in kidneys during pre- and postnatal development. RESULTS: All the protein levels of PDGFR-alpha and -beta and the mRNA levels of PDGF-C and D were high in kidneys during the prenatal period and decreased differently during the postnatal period. PDGFR-alpha was expressed in the interstitial space at embryo day 18. PDGFR-beta protein were expressed in metanephric blastema at embryo day 18. PDGF-C mRNA was expressed in metanephric blastema, developing glomerulus at embryo 18 day and in collecting duct at postnatal day 7. PDGF-D mRNA was expressed in the parietal and vesceral epithelial cells during pre and postnatal period. CONCLUSION: These results indicate that the PDGF subtypes (C & D) and their receptors (PDGFR-alpha & -beta) are differently expressed in the kidney during the prenatal and postnatal period.
Embryonic Structures
;
Epithelial Cells
;
Humans
;
Kidney
;
Platelet-Derived Growth Factor
;
Rabeprazole
;
Receptors, Platelet-Derived Growth Factor*
;
RNA, Messenger
9.Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1.
Chinese Journal of Pathology 2012;41(11):779-783
Animals
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Eosinophilia
;
genetics
;
pathology
;
Gene Rearrangement
;
Humans
;
Lymphoma
;
genetics
;
pathology
;
Myeloproliferative Disorders
;
genetics
;
pathology
;
Receptor, Fibroblast Growth Factor, Type 1
;
genetics
;
Receptor, Platelet-Derived Growth Factor alpha
;
genetics
;
Receptor, Platelet-Derived Growth Factor beta
;
genetics
10.Single CD271 marker isolates mesenchymal stem cells from human dental pulp.
Ruth ALVAREZ ; Hye-Lim LEE ; Christine HONG ; Cun-Yu WANG
International Journal of Oral Science 2015;7(4):205-212
Mesenchymal stem cells (MSCs) are a promising tool in regenerative medicine due to their capacity to differentiate into multiple lineages. In addition to MSCs isolated from bone marrow (BMSCs), adult MSCs are isolated from craniofacial tissues including dental pulp tissues (DPs) using various stem cell surface markers. However, there has been a lack of consensus on a set of surface makers that are reproducibly effective at isolating putative multipotent dental mesenchymal stem cells (DMSCs). In this study, we used different combinations of surface markers (CD51/CD140α, CD271, and STRO-1/CD146) to isolate homogeneous populations of DMSCs from heterogeneous dental pulp cells (DPCs) obtained from DP and compared their capacity to undergo multilineage differentiation. Fluorescence-activated cell sorting revealed that 27.3% of DPCs were CD51(+)/CD140α(+), 10.6% were CD271(+), and 0.3% were STRO-1(+)/CD146(+). Under odontogenic conditions, all three subsets of isolated DMSCs exhibited differentiation capacity into odontogenic lineages. Among these isolated subsets of DMSCs, CD271(+) DMSCs demonstrated the greatest odontogenic potential. While all three combinations of surface markers in this study successfully isolated DMSCs from DPCs, the single CD271 marker presents the most effective stem cell surface marker for identification of DMSCs with high odontogenic potential. Isolated CD271(+) DMSCs could potentially be utilized for future clinical applications in dentistry and regenerative medicine.
Adult
;
Adult Stem Cells
;
cytology
;
Antigens, CD
;
analysis
;
Antigens, Surface
;
analysis
;
Biomarkers
;
analysis
;
CD146 Antigen
;
analysis
;
Cell Culture Techniques
;
Cell Differentiation
;
physiology
;
Cell Lineage
;
Cell Separation
;
methods
;
Cells, Cultured
;
Chondrogenesis
;
physiology
;
Dental Pulp
;
cytology
;
Flow Cytometry
;
methods
;
Humans
;
Integrin alphaV
;
analysis
;
Mesenchymal Stromal Cells
;
cytology
;
Multipotent Stem Cells
;
cytology
;
Nerve Tissue Proteins
;
analysis
;
Odontogenesis
;
physiology
;
Receptor, Platelet-Derived Growth Factor alpha
;
analysis
;
Receptors, Nerve Growth Factor
;
analysis