K-RAS and N-RAS mutations in testicular germ cell tumors

Hacioglu, Bekir; Kodaz, Hilmi; Erdoğan, Bülent; Cinkaya, Ahmet; Taştekin, Ebru; Hacıbekiroğlu, İlhan; Türkmen, Esma; Köstek, Osman; Uzunoğlu, Sernaz; Çiçin, İrfan

doi:10.17305/bjbms.2017.1764

Cited by 13 publications

(15 citation statements)

References 16 publications

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“…Among the numerous genetic and environmental factors, cryptorchidism is the most common risk factor. Compared to the noted KRAS and NRAS mutations in TGCTs [286], the overall genetic alterations frequency of PIK3CA (3%), PIK3R1 (1.3%), AKT1 (0.7%) and PTEN (0.7%) are much less, even though mutations in PIK3CA and AKT1 are observed exclusively in cisplatin-resistant TGCTs [287]. AXIN1, TDRG1 and LncRNA H19 regulate cell viability, apoptosis or cisplatin resistance via the PI3K/ AKT/mTOR signaling pathway [288][289][290].…”

Section: Dysregulation Of the Pi3k/akt Pathway In The Genitourinary Smentioning

confidence: 92%

Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

et al. 2020

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Given that the PI3K/AKT pathway has manifested its compelling influence on multiple cellular process, we further review the roles of hyperactivation of PI3K/AKT pathway in various human cancers. We state the abnormalities of PI3K/AKT pathway in different cancers, which are closely related with tumorigenesis, proliferation, growth, apoptosis, invasion, metastasis, epithelial-mesenchymal transition, stem-like phenotype, immune microenvironment and drug resistance of cancer cells. In addition, we investigated the current clinical trials of inhibitors against PI3K/AKT pathway in cancers and found that the clinical efficacy of these inhibitors as monotherapy has so far been limited despite of the promising preclinical activity, which means combinations of targeted therapy may achieve better efficacies in cancers. In short, we hope to feature PI3K/ AKT pathway in cancers to the clinic and bring the new promising to patients for targeted therapies.

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Section: Dysregulation Of the Pi3k/akt Pathway In The Genitourinary Smentioning

confidence: 92%

Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

et al. 2020

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“…We used western blotting to detect the activation of the Ras/ Raf/MEK/Erk signaling pathway; the results indicated that HNRNPC knockdown significantly inhibited the activation of the MAPK signaling pathway. Ras mutation has a very important role in many cancers (63)(64)(65), and HCC is no exception (66,67). Both H-ras and K-ras have respective splice variants (68,69), which could be regarded as Ras mutations at the mRNA level.…”

Section: Discussionmentioning

confidence: 99%

Suppression of Heterogeneous Nuclear Ribonucleoprotein C Inhibit Hepatocellular Carcinoma Proliferation, Migration, and Invasion via Ras/MAPK Signaling Pathway

Cai

Zhang

et al. 2021

Front. Oncol.

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Hepatocellular carcinoma (HCC), the most common malignant tumor, has high fatality and recurrence rates. Accumulating evidence shows that heterogeneous nuclear ribonucleoprotein C (HNRNPC), which is mainly involved in RNA splicing, export, and translation, promotes progression and metastasis of multiple tumor types; however, the effects of HNRNPC in HCC are unknown. In the present study, high levels of HNRNPC were detected in tumor tissues compared with para-tumor tissues by immunohistochemical and western blot assays. Furthermore, Cox proportional hazards regression models, the Kaplan–Meier method, and clinicopathologic features analysis showed that HNRNPC was not only an independent prognostic factor for both overall and disease-free survival in HCC but also a predictor of large tumor size and advanced tumor stage. Functional experiments revealed that silencing of HNRNPC not only led to arrest of more HCC cells at G0/G1 phase to inhibit their proliferation, but also suppressed EMT process to block their invasion, and migration in vitro; this was related to the Ras/MAPK signaling pathway. In addition, blocking of HCC cell proliferation regulated by HNRNPC silencing was observed in vivo. Finally, rescue tests showed that after recovery of Ras/MAPK signaling pathway activity by treatment with Ras agonists, the proliferation, migration, and invasion suppression of Huh-7 and Hep 3B cell lines caused by HNRNPC knockdown was partially reversed. Taken together, these results indicate that HNRNPC knockdown inhibits HCC cell proliferation, migration and invasion, in part via the Ras/MAPK signaling pathway. Thus, HNRNPC may have an important role in the progression of HCC and represents a promising biomarker for evaluation of prognosis and a potential therapeutic target in HCC patients.

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“…20 Of interest, IKBKB has been associated with KRAS, which is a known oncogene linked to GCTs. 21 The de novo analysis identified 14 rare variants within proband one across 10 unique genes ( Table 1). Nine of the variants had known RefSeq (rs#) identification numbers in the dbSNP database and MAF of >0.01 in the gnomAD genome database as well as within the…”

Section: Dovepressmentioning

confidence: 99%

<p>Germline Sequencing Identifies Rare Variants in Finnish Subjects with Familial Germ Cell Tumors</p>

Crowgey¹,

Soini²,

Shah³

et al. 2020

TACG

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Purpose: Pediatric germ cell tumors are rare, representing about 3% of childhood malignancies in children less than 15 years of age, presenting in neonates or adolescents with a greater incidence noted in older adolescents. Aberrations in primordial germ cell proliferation/differentiation can lead to a variety of neoplasms, including teratomas, embryonal carcinoma, choriocarcinoma, and yolk sac tumors. Patients and Methods: Three Finnish families with varying familial germ cell tumors were identified, and whole-genome sequencing was performed using an Illumina sequencing platform. In total, 22 unique subjects across the three families were sequenced. Family 1 proband (female) was affected by malignant ovarian teratoma, Family 2 proband (female) was affected by sacrococcygeal teratoma with yolk sac tumor in the setting of Cornelia de Lange syndrome, and Family 3 proband (male) was affected by malignant testicular teratoma. Rare variants were identified using an autosomal recessive or de novo model of inheritance. Results: For family 1 proband (female), an autosomal recessive or de novo model of inheritance identified variants of interest in the following genes: CD109, IKBKB, and CTNNA3, SUPT6H, MUC5AC, and FRG1. Family 2 proband (female) analysis identified gene variants of interest in the following genes: LONRF2, ANO7, HS6ST1, PRB2, and DNM2. Family 3 proband (male) analysis identified the following potential genes: CRIPAK, KRTAP5-7, and CACNA1B. Conclusion: Leveraging deep pedigrees and next-generation sequencing, rare germline variants were identified that were enriched in three families from Finland with a history of familial germ cell tumors. The data presented support the importance of germline mutations when analyzing complex cancers with a low somatic mutation landscape.

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K-RAS and N-RAS mutations in testicular germ cell tumors

Cited by 13 publications

References 16 publications

Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

Suppression of Heterogeneous Nuclear Ribonucleoprotein C Inhibit Hepatocellular Carcinoma Proliferation, Migration, and Invasion via Ras/MAPK Signaling Pathway

<p>Germline Sequencing Identifies Rare Variants in Finnish Subjects with Familial Germ Cell Tumors</p>

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