The Predisposing Gene of the Eker Rat Inherited Cancer Syndrome Is Tightly Linked to the Tuberous Sclerosis (TSC2) Gene

1994 ◽  
Vol 203 (2) ◽  
pp. 1302-1308 ◽  
Author(s):  
O. Hino ◽  
T. Kobayashi ◽  
H. Tsuchiya ◽  
Y. Kikuchi ◽  
E. Kobayashi ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tsc2 Gene ◽  
Cancer Syndrome ◽  
Inherited Cancer ◽  
Eker Rat ◽  
Inherited Cancer Syndrome

A germline insertion in the tuberous sclerosis (Tsc2) gene gives rise to the Eker rat model of dominantly inherited cancer

1995 ◽  
Vol 9 (1) ◽  
pp. 70-74 ◽  
Author(s):  
Toshiyuki Kobayashi ◽  
Youko Hirayama ◽  
Etsuko Kobayashi ◽  
Yoshiaki Kubo ◽  
Okio Hino
Keyword(s):  
Tuberous Sclerosis ◽  
Rat Model ◽  
Tsc2 Gene ◽  
Inherited Cancer ◽  
Eker Rat

Cancer predisposing germline mutations in patients (pts) with urothelial cancer (UC) of the renal pelvis (R-P), ureter (U) and bladder (B).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4510-4510 ◽  
Author(s):  
Maria Isabel Carlo ◽  
Liying Zhang ◽  
Diana Mandelker ◽  
Joseph Vijai ◽  
Catharine Kline Cipolla ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Germline Mutations ◽  
Germline Gene ◽  
Repair Pathway ◽  
Cancer Syndrome ◽  
Full Spectrum ◽  
Inherited Cancer ◽  
Hereditary Component ◽  
History Of ◽  
Inherited Cancer Syndrome

4510 Background: Urothelial cancers (UC) are suspected to have a substantial hereditary component, but other than highly penetrant genes such as those in mismatch-repair pathway (e.g. MSH2) typically associated with R-P/U primaries, heritable gene mutations have not been systematically studied. We sought to investigate the prevalence of known cancer pre-disposing germline mutations in pts with UC originating from all sites within the urinary tract. Methods: Pts with R-P, U and B primaries, unselected for suspicion of inherited cancer syndrome, were prospectively enrolled from medical oncology and urology clinics to a germline sequencing protocol from June 2016 to January 2017. Germline gene analysis was performed in a CLIA-certified lab using a next generation sequencing (NGS) platform (MSK-IMPACT) that analyzes tumor-normal DNA pairs. The germline gene panel consisted of 76 genes associated with hereditary cancer predisposition. Results: As of January 24, 2017, 101 pts have NGS results available, with median age 63 (31-87), 76% male, 24% female. Primary sites were B (67%), R-P/U (31%), or both (3%). 73% had organ-confined disease and 27% had metastases. 8% had early onset (≤45 yrs at diagnosis), 10% had a family history of UC, 25% had documented non-UC cancers. 25 pathogenic or likely pathogenic (P-LP) mutations were identified in 22 patients. P-LP mutations were present in 29% of pts with R-P/U primaries and 18% of pts with B primaries. 12 DNA damage response gene alterations were found (4 CHEK2, 3 BRCA1, 2 BRCA2, 1 ATM, 1 BRIP1, 1 NBN) and 8 in Lynch syndrome associated genes (5 MSH2, 2 MSH6, 1 MLH1). Other mutations include 2 APC, 1 TP53, and 1 FH. Notably 3 pts had 2 alterations each ( MSH6/ APC, BRCA2/ APC, BRCA1/ CHEK2). 9/22 pts with P-LP mutations did not meet American College of Medical Genetics criteria for genetic screening. Conclusions: 22% of UC pts had a germline mutation in a cancer-associated gene. There was an unexpectedly high frequency of pts with DNA-repair pathway mutations. Active accrual is ongoing to define the full spectrum of alterations. These results have profound implications for genetic counseling and screening and further studies are warranted.

scholarly journals Familial/inherited cancer syndrome: a focus on the highly consanguineous Arab population

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Fawz S. AlHarthi ◽  
Alya Qari ◽  
Alaa Edress ◽  
Malak Abedalthagafi
Keyword(s):  
Cancer Syndrome ◽  
Arab Population ◽  
Inherited Cancer ◽  
Inherited Cancer Syndrome

scholarly journals Hereditary Diffuse Gastric Cancer: Multidisciplinary Case Report with Review of the Literature

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Rebecca Wilcox ◽  
Melody Perpich ◽  
Amy Noffsinger ◽  
Mitchell C. Posner ◽  
Kumarasen Cooper
Keyword(s):  
Gastric Cancer ◽  
Case Report ◽  
Hereditary Diffuse Gastric Cancer ◽  
Diffuse Gastric Cancer ◽  
Review Of The Literature ◽  
Cancer Syndrome ◽  
Inherited Cancer ◽  
Prophylactic Gastrectomy ◽  
Signet Ring ◽  
Inherited Cancer Syndrome

Hereditary diffuse gastric cancer (HDGC) is a rare, inherited cancer syndrome with at least one fourth of HDGC patients having an autosomal dominantly inherited mutation of CDH1 (E-Cadherin). Penetrance is relatively high (70–80% lifetime risk for gastric cancer). It is important for pathologists to recognize the syndrome's phenotype in early gastric lesions: patchy intramucosal signet ring cells often associated with pagetoid spread. Due to the insidious nature of this lesion, surveillance is limited and currently prophylactic gastrectomy is an option chosen by many HDGC patients. We present a case report from a multidisciplinary team of authors with a review of the literature that includes the updated guidelines for CDH1 genetic testing.

TSC2 Gene Mutant (Eker) Rat Model of a Mendelian Dominantly Inherited Cancer

1999 ◽  
pp. 95-108 ◽  
Author(s):  
O. Hino ◽  
T. Fukuda ◽  
N. Satake ◽  
T. Kobayashi ◽  
S. Honda ◽  
...  
Keyword(s):  
Rat Model ◽  
Tsc2 Gene ◽  
Inherited Cancer ◽  
Gene Mutant ◽  
Eker Rat

scholarly journals Progress toward Understanding Epileptogenesis in Tuberous Sclerosis Complex: Two Hits, No Outs, and the Eker Rat is up to Bat

2005 ◽  
Vol 5 (4) ◽  
pp. 136-138 ◽  
Author(s):  
Carl E. Stafstrom
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Rat Model ◽  
Tuber Formation ◽  
Cresyl Violet ◽  
Tsc2 Gene ◽  
Tissue Sections ◽  
Eker Rat ◽  
Cortical Tubers ◽  
Dysmorphic Neurons

Abnormal Cortical Cells and Astrocytomas in the Eker Rat Model of Tuberous Sclerosis Complex Takahashi DK, Dinday MT, Barbaro NM, Baraban SC Epilepsia 2004;45:1525–1530 Purpose In patients with tuberous sclerosis complex (TSC), a wide range of neurologic abnormalities develop, including mental retardation and seizures. Brains from TSC patients are characterized by the presence of cortical tubers, large dysmorphic neurons, and abnormal cytomegalic cells. Although analysis of human TSC brain samples led to the identification of these abnormal cell types, very little is known about how these cells function. In an effort to model TSC-associated CNS abnormalities (and ultimately to analyze the electrophysiologic properties of abnormal cells), we examined Eker rats carrying a Tsc2 mutation. Anatomic studies, including standard histologic stains and immunocytochemistry, were performed on young Eker rats exposed to a carcinogen in utero or on aged untreated Eker rats (18–24 months old). Methods Pregnant TSC2+/– females were injected once a day with hydroquinone, and offspring were killed at postnatal day P14 or P28. Coronal tissue sections throughout the CNS were prepared and stained for cresyl violet. In separate studies, brains of old untreated Eker rats were sectioned for anatomic analysis by using standard immunohistochemical techniques. Results Tissue sections stained with cresyl violet did not reveal any gross differences between hydroquinonetreated Eker ( Tsc2 Ek/+) rats and siblings ( Tsc2+/+). However, two classes of abnormal giant cells were observed in brain sections from untreated aged Eker rats: 1) large dysmorphic pyramid-like cells immunoreactive for NeuN, tuberin, and EAAC-1 in layers IV to VI; and 2) abnormal cytomegalic cells immunoreactive for glial fibrillary acidic protein, vimentin, and nestin in deep cortical layers or along the white matter. In addition, large subependymal astrocytomas were observed in four animals. Conclusions Our data suggest that cortical tuber formation in Eker rats is a rare event and that prenatal exposure to a nongenotoxic carcinogen such as hydroquinone is not sufficient to induce tuber formation. However, with advanced age, an increased likelihood of astrocytoma formation and the emergence of dysmorphic neurons and cytomegalic cells in the Eker rat brain might exist; each of these abnormalities mimics those seen clinically and could contribute to neurologic problems associated with TSC. Further analysis of this rodent model may be warranted. Morphology of Cerebral Lesions in the Eker Rat Model of Tuberous Sclerosis Wenzel HJ, Patel LS, Robbins CA, Emmi A, Yeung RS, Schwartzkroin PA Acta Neuropathol (Berl) 2004;108:97–108 Tuberous sclerosis (TSC) is an autosomal dominant disorder, caused by mutations of either the TSC1 or TSC2 gene. Characteristic brain pathologies (including cortical tubers and subependymal hamartomas/giant astrocytomas) are thought to cause epilepsy, as well as other neurologic dysfunction. The Eker rat, which carries a spontaneous germline mutation of the TSC2 gene ( Tsc2+/+), provides a unique animal model in which to study the relation between TSC cortical pathologies and epilepsy. In the present study, we analyzed the seizure propensity and histopathologic features of a modified Eker rat preparation, in which early postnatal irradiation was used as a “second hit” stimulus in an attempt to exacerbate cortical malformations and increase seizure propensity. Irradiated Eker rats had a tendency toward lower seizure thresholds (latencies to flurothyl-induced seizures) than seen in nonirradiated Eker rats (significant difference) or irradiated wild-type rats (nonsignificant difference). The majority of irradiated Eker rats exhibited dysplastic cytomegalic neurons and giant astrocyte-like cells, similar to cytopathologies observed in TSC lesions of patients. The most prominent features in these brains were hamartoma-like lesions involving large eosinophilic cells, similar to giant tuber cells in human TSC. In some cells from these hamartomas, immunocytochemistry revealed features of both neuronal and glial phenotypes, suggesting an undifferentiated or immature cell population. Both normal-appearing and dysmorphic neurons, as well as cells in the hamartomas, exhibited immunopositivity for tuberin, the protein product of the TSC2 gene.

E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer

1999 ◽  
Vol 14 (3) ◽  
pp. 249-255 ◽  
Author(s):  
Parry J. Guilford ◽  
Justin B.W. Hopkins ◽  
William M. Grady ◽  
Sanford D. Markowitz ◽  
Joseph Willis ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Germline Mutations ◽  
Diffuse Gastric Cancer ◽  
Cancer Syndrome ◽  
Inherited Cancer ◽  
Inherited Cancer Syndrome ◽  
E Cadherin
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