Comparison analysis of Baso Cellular Carcinoma and Spino Cellular Carcinoma - Protein Kinase D1, Wnt/β-catenin and Epithelial to Mesenchimal Transition (markers)

Understanding cancer biology is crucial to the successful diagnosis and application of personalized therapies. Skin carcinogenesis is a multi-step process. The first step is the development of potentially malignant disorders (PMDs) known as leukoplakia, erytroplakia, lichen planus, probably trough mutation in the proteins regulated cell cycle (p16INK4A, p21Waf1/Cip1/Sdi1, p27 kip1, Cyclin D1) and, second in p53 (TP53), Ras, hTert, EGFR, will reverse benign phenotype of late precancer lesions (PMDs) into benign cancer lesion. Third mutation probably in PI3K, PKD1 or E-cadherin, will increase malignant potential of SCCs, activating EMTransition, invasion and metastasis, e.g. aggressive phenotype. In BCC mutations of p53 are known to be late events (UV signature), whereas silencing of 14-3-3 takes place early in tumor progression, concomitant with increased activity of Snail. Early increased expression of PKD1 and down-regulation of c-myc mRNA are also events in pathogenesis of BCC. There is no data for detected mutations in PKD1 gene in both cancers, although the kinases is with high expression in BCC and lack of expression in SCC. There is no data concerning PKD1 expression in the PMDs leading to SCCs, nor to BCCs, such data were recently published concerning PKD1 expression in pancreatic oncogenesis. Curently adequate question is whether lack of PKD1 expression in SCCs, despite its PMDs origin, is a consequence of its spinous layer origin, or is a consequense of PKD1 gene mutations (downregulation). Identification of mutations as markers for early malignant transformation could be useful for early diagnosis and treatment of skin head and neck cancers.

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Identification of Somatically Acquired Gene Mutations In the Kineome and Exome In CLL

Blood ◽

10.1182/blood.v116.21.2410.2410 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2410-2410

Author(s):

Xiaosong Zhang ◽

Meng Li ◽

Peter Ouillette ◽

Luis Diaz ◽

Marcelo Reis ◽

...

Keyword(s):

Cancer Biology ◽

Conflicts Of Interest ◽

Single Gene ◽

Gene Mutations ◽

P53 Mutations ◽

Kinase Gene ◽

Immunoglobulin Receptor ◽

Paired Samples ◽

Exon Capture ◽

Exome Sequence

Abstract Abstract 2410 The pathogenesis of CLL remains incompletely understood. While acquired chromosomal aberrations have been demonstrated to influence CLL biology and clinical behavior, it remains unclear what single gene defects other than p53 or ATM mutations contribute to or cause the CLL phenotype. In particular, recurrent gene mutations that are increasingly found in other hematological malignancies have not yet been identified in CLL. Further, the discovery of stereotypical immunoglobulin receptor genes in CLL has been advanced in support of the involvement of autoantigenes in the pathogenesis of CLL and thus a pro-proliferative or anti-apoptotic gene mutation may possibly not exist in CLL. Given that kinase genes are often the targets for recurrent gene mutations and given the prospect for identification of drugable targets, we have analyzed 515 kinase genes in a discovery panel of 23 well characterized CLL samples (in DNA from CD19+ sorted cells) and tested their somatic nature in CD3+ cell-derived DNA from the same patients. A total of 8308 different exon sequences were analyzed. We identified six individual kinase gene mutations (WEE1, NEK1, BRAF, KDR, MAP4K3 and TRPM6), each occurring once in a separate CLL case as well as >1450 non-synonymous polymorphisms but no recurrent kinase gene mutations were identified. Interestingly, mutations in all these genes but NEK1 had previously been identified in cancer genome projects of cancers of the breast, colorectum, pancreas and glioblastome multiforme and WEE1, BRAF and KDR have established roles in cancer biology. Next we used solution exon capture of genomic DNA followed by Solexa-based next gen exome sequencing on 8 paired CLL derived DNA samples (FACS-sorted CD19+ versus CD3+ paired samples), including 2 samples with known p53 mutations. Using stringent criteria for mutation calling, we identified 69 mutated genes including the 2 cases of p53 mutations. None of the mutated genes were recurrent. Work is in progress to estimate the frequency of mutations in these genes in a wider panel of CLL cases. In summary, our data provide practical information about the mutations state of the CLL kineome and exome with implications for CLL biology/pathogenesis. This data should motivate additional exome sequence analyses of more CLL samples to fully capture and describe the mutation load in CLL. Disclosures: No relevant conflicts of interest to declare.

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ALAS2 acts as a modifier gene in patients with congenital erythropoietic porphyria

Blood ◽

10.1182/blood-2011-03-342873 ◽

2011 ◽

Vol 118 (6) ◽

pp. 1443-1451 ◽

Cited By ~ 56

Author(s):

Jordi To-Figueras ◽

Sarah Ducamp ◽

Jerome Clayton ◽

Celia Badenas ◽

Constance Delaby ◽

...

Keyword(s):

Autosomal Recessive ◽

Gene Mutations ◽

Wild Type ◽

Aminolevulinate Synthase ◽

Sequence Variations ◽

Congenital Erythropoietic Porphyria ◽

New Type ◽

Terminal Amino ◽

Exon 11 ◽

Increased Activity

AbstractMutations in the uroporphyrinogen III synthase (UROS) gene cause congenital erythropoietic porphyria (CEP), an autosomal-recessive inborn error of erythroid heme biosynthesis. Clinical features of CEP include dermatologic and hematologic abnormalities of variable severity. The discovery of a new type of erythroid porphyria, X-linked dominant protoporphyria (XLDPP), which results from increased activity of 5-aminolevulinate synthase 2 (ALAS2), the rate-controlling enzyme of erythroid heme synthesis, led us to hypothesize that the CEP phenotype may be modulated by sequence variations in the ALAS2 gene. We genotyped ALAS2 in 4 unrelated CEP patients exhibiting the same C73R/P248Q UROS genotype. The most severe of the CEP patients, a young girl, proved to be heterozygous for a novel ALAS2 mutation: c.1757 A > T in exon 11. This mutation is predicted to affect the highly conserved and penultimate C-terminal amino acid of ALAS2 (Y586). The rate of 5-aminolevulinate release from Y586F was significantly increased over that of wild-type ALAS2. The contribution of the ALAS2 gain-of-function mutation to the CEP phenotype underscores the importance of modifier genes underlying CEP. We propose that ALAS2 gene mutations should be considered not only as causative of X-linked sideroblastic anemia (XLSA) and XLDPP but may also modulate gene function in other erythropoietic disorders.

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Case Report of Atypical Juxtaglomerular Cell Tumor

Case Reports in Pathology ◽

10.1155/2018/6407360 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Satoru Munakata ◽

Eisuke Tomiyama ◽

Hitoshi Takayama

Keyword(s):

Tumor Cells ◽

Gene Mutations ◽

Massive Hemorrhage ◽

Cell Tumor ◽

Lower Portion ◽

Juxtaglomerular Cell ◽

Eosinophilic Cytoplasm ◽

Potentially Malignant ◽

Juxtaglomerular Cell Tumor ◽

The Right

Juxtaglomerular cell tumor (JGCT) is a rare renal tumor, producing renin and behaving almost in a benign fashion. So far, only three cases have been reported as malignant. We report a rare case with atypical JGCT. A 74-year-old male was referred to our hospital due to hypertension, proteinuria, and hematuria. Abdominal CT revealed a mass measured in 9.7×7.0 cm in the lower portion of the right kidney. Right kidney was removed laparoscopically. Grossly, white to tan tumor with massive hemorrhage and necrosis occupied the lower portion of the right kidney. Microscopically, tumor grew in a solid fashion. Tumor cells were polygonal to ovoid cells with round nuclei and clear to eosinophilic cytoplasm. Mitosis was found in 5 per 10 HPF. Immunohistochemically, tumor cells were stained by vimentin and CD34. Some tumor cells were also positive for renin. Electron micrograph showed near rhomboid crystalline structure in the tumor cells. Because of massive necrosis and mitotic figures, diagnosis of atypical (potentially malignant) JGCT was rendered. Gene mutations for IDH1, PIK3CA, K-ras, N-ras, Braf, and EGFR were not found by MBP-QP system.

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Identification of missense and synonymous variants in Iranian patients suffering from autosomal dominant polycystic kidney disease

10.21203/rs.2.18544/v2 ◽

2020 ◽

Author(s):

Fatemeh Khadangi ◽

Adam Torkamanzehi ◽

Mohammad Amin Kerachian

Keyword(s):

Kidney Disease ◽

Genetic Analysis ◽

Autosomal Dominant ◽

Molecular Genetic ◽

Gene Mutations ◽

Molecular Genetic Analysis ◽

Polycystic Kidney ◽

Pkd1 Gene ◽

Autosomal Dominant Polycystic Kidney ◽

Iranian Patients

Abstract Background: Autosomal dominant polycystic kidney disease (ADPKD), the predominant type of inherited kidney disorder, occurs due to PKD1 and PKD2 gene mutations. ADPKD diagnosis is made primarily by kidney imaging. However, molecular genetic analysis is required to confirm the diagnosis. It is critical to perform a molecular genetic analysis when the imaging diagnosis is uncertain, particularly in simplex cases (i.e., a single occurrence in a family), in people with remarkably mild symptoms, or in individuals with atypical presentations. The main aim of this study is to determine the frequency of PKD1 gene mutations in Iranian patients with ADPKD diagnosis. Methods: Genomic DNA was extracted from blood samples from 22 ADPKD patients, who were referred to the Qaem Hospital in Mashhad, Iran. By using appropriate primers, 16 end exons of PKD1 gene that are regional hotspots, were replicated with PCR. Then, PCR products were subjected to DNA directional Sanger sequencing. Results: The DNA sequencing in the patients has shown that exons 35, 36 and 37 were non- polymorphic, and that most mutations had occurred in exons 44 and 45. In two patients, an exon-intron boundary mutation had occurred in intron 44. Most of the variants were missense and non-synonymous types. Conclusion: In the present study, we have shown the occurrence of nine novel missense or synonymous variants in PKD1 gene. These data could contribute to an improved diagnostic and genetic counseling in clinical settings.

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Bridging Cancer Biology with the Clinic: Comprehending and Exploiting IDH Gene Mutations in Gliomas

Cancer Genomics & Proteomics ◽

10.21873/cgp.20101 ◽

2018 ◽

Vol 15 (5) ◽

pp. 421-436 ◽

Cited By ~ 2

Author(s):

OURANIA ROMANIDOU ◽

VASSILIKI KOTOULA ◽

GEORGE FOUNTZILAS

Keyword(s):

Cancer Biology ◽

Gene Mutations

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Stress and DNA repair biology of the Fanconi anemia pathway

Blood ◽

10.1182/blood-2014-04-526293 ◽

2014 ◽

Vol 124 (18) ◽

pp. 2812-2819 ◽

Cited By ~ 44

Author(s):

Simonne Longerich ◽

Jian Li ◽

Yong Xiong ◽

Patrick Sung ◽

Gary M. Kupfer

Keyword(s):

Dna Repair ◽

Fanconi Anemia ◽

Cancer Biology ◽

Excision Repair ◽

Genetic Diseases ◽

Gene Mutations ◽

Interaction Network ◽

Cancer Genes ◽

Dna Mismatch ◽

Rare Genetic Diseases

Abstract Fanconi anemia (FA) represents a paradigm of rare genetic diseases, where the quest for cause and cure has led to seminal discoveries in cancer biology. Although a total of 16 FA genes have been identified thus far, the biochemical function of many of the FA proteins remains to be elucidated. FA is rare, yet the fact that 5 FA genes are in fact familial breast cancer genes and FA gene mutations are found frequently in sporadic cancers suggest wider applicability in hematopoiesis and oncology. Establishing the interaction network involving the FA proteins and their associated partners has revealed an intersection of FA with several DNA repair pathways, including homologous recombination, DNA mismatch repair, nucleotide excision repair, and translesion DNA synthesis. Importantly, recent studies have shown a major involvement of the FA pathway in the tolerance of reactive aldehydes. Moreover, despite improved outcomes in stem cell transplantation in the treatment of FA, many challenges remain in patient care.

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Prognostic value of the PIK3CA, AKT, and PTEN mutations in oral squamous cell carcinoma: literature review

Archives of Medical Science ◽

10.5114/aoms.2020.100780 ◽

2021 ◽

Vol 17 (1) ◽

pp. 207-217

Author(s):

Anna Starzyńska ◽

Aleksandra Sejda ◽

Paulina Adamska ◽

Giulia Marvaso ◽

Monika Sakowicz-Burkiewicz ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cancer Biology ◽

Gene Mutations ◽

Phosphatidyl Inositol ◽

Serine Threonine Kinase ◽

Main Components ◽

Phosphatase And Tensin Homologue

Over 260,000 (2013) new oral squamous cell carcinoma (OSCC) cases are reported annually worldwide. Despite development in OSCC management, the outcome is still unsatisfactory. Identification of new molecular markers may be of use in prevention, prognosis, and choice of an appropriate therapy.The intracellular molecular signalling pathway of phosphatidyl-inositol-3-kinase is involved in the process of cell growth, differentiation, migration, and survival. The main components of this pathway: PIK3CA (phosphatidylinositol-4,5-bisphosphate-3-kinase catalytic subunit ), PTEN (phosphatase and tensin homologue deleted on chromosome 10), and AKT (serine-threonine kinase) are potential objects of research when introducing new therapeutic agents. The aim of this paper is to evaluate the PIK3CA, PTEN, and AKT gene mutations as prognostic factors in OSCC and to describe their role in aggressive disease progression. This is crucial for oral cancer biology understanding and for indicating which direction new clinical treatments should take.

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Functional information from magnetic resonance imaging

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100136799 ◽

1995 ◽

Vol 53 ◽

pp. 84-85

Author(s):

Alan P. Koretsky ◽

Afonso Costa e Silva ◽

Yi-Jen Lin

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

High Resolution ◽

Cancer Biology ◽

Imaging Modality ◽

Magnetic Resonance Images ◽

Great Success ◽

Functional Information ◽

Resonance Imaging ◽

High Resolution Mri

Magnetic resonance imaging (MRI) has become established as an important imaging modality for the clinical management of disease. This is primarily due to the great tissue contrast inherent in magnetic resonance images of normal and diseased organs. Due to the wide availability of high field magnets and the ability to generate large and rapidly switched magnetic field gradients there is growing interest in applying high resolution MRI to obtain microscopic information. This symposium on MRI microscopy highlights new developments that are leading to increased resolution. The application of high resolution MRI to significant problems in developmental biology and cancer biology will illustrate the potential of these techniques.In combination with a growing interest in obtaining high resolution MRI there is also a growing interest in obtaining functional information from MRI. The great success of MRI in clinical applications is due to the inherent contrast obtained from different tissues leading to anatomical information.

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