Targeted Next-Generation Sequencing of Cancer Genes in Advanced Stage Malignant Pleural Mesothelioma: A Retrospective Study

Iacono, Marco Lo; Monica, Valentina; Righi, Luisella; Grosso, Federica; Libener, Roberta; Vatrano, Simona; Bironzo, Paolo; Novello, Silvia; Musmeci, Loredana; Volante, Marco; Papotti, Mauro; Scagliotti, Giorgio Vittorio

doi:10.1097/jto.0000000000000436

Cited by 140 publications

(159 citation statements)

References 26 publications

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“…A 10% mutation frequency of KDR gene has been reported [8]. Another study reported a frequency of 38/123 patients (30.9%) with mutation in KDR gene in Malignant Pleural Mesothelioma [9]. It is noteworthy to mention here that, a study on non-small cell lung cancer reported high Q472H type of KDR mutation number in 33.3% patients [10] and in another study, it has been suggested to play a role of proto-oncogene in Lung Adeno-carcinoma [11].…”

Section: Discussionmentioning

confidence: 99%

KDR Mutation: A High-Frequency Rare Mutation and its Correlation with other Somatic Mutations in Indian Colorectal Cancer Patients

Jauhri¹,

Gupta²,

Shokeen³

et al. 2017

Next Generat Sequenc & Applic

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Aim: This study aims to find out the frequency of KDR mutation in colorectal cancer patients and if any correlation exists between KDR mutation and demographical features or with other common and uncommon gene mutations occurring in colon cancer.Methods: FFPE samples of 112 patients were analyzed using next generation sequencing.Results: KDR gene was found to be mutated most frequently (19.6%) as compared to other uncommon gene mutations occurring among patients. 21/22 patients had the p.Q472H type of KDR mutation. It was significantly associated with mutations in PTEN (p=0.003), KRAS (p=0.026), APC (p=0.033), EGFR (p=0.036), NOTCH1 (p=0.029) and ERBB4 (p=0.008) mutations. More number of males (22.06%) harbored KDR mutations than the number of females (15.9%). A higher number of KDR mutations in Stage III (31%) as compared to other stages -I-II (19.23%) and IV (7.31%) was reported. KDR mutations were found to be in greater number in patients with lymph node metastasis (27.3%) as compared to liver metastasis (8%). However, a statistically significant association of any clinical parameter was not found. Conclusion:Our results suggest that although KDR is a rare somatic mutation in CRC, it plays a pivotal role in the development of colon cancer via angiogenesis pathway.

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Section: Discussionmentioning

confidence: 99%

KDR Mutation: A High-Frequency Rare Mutation and its Correlation with other Somatic Mutations in Indian Colorectal Cancer Patients

Jauhri¹,

Gupta²,

Shokeen³

et al. 2017

Next Generat Sequenc & Applic

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“…However, large deletions of BAP1 have never been detected in germline configuration in families either with multiple MM [3,9,11,[32][33][34][35][36][37] or without MM [26,28,29]. The loss of nuclear BAP1 immunostaining suggests that these tumors may harbor somatic alterations of the BAP1 gene, a frequent event in sporadic epithelial MM [21,24,26,27]. Although most BAP1 somatic mutations are nucleotide-level mutations, additional technical approaches would have been necessary to detect gross deletions at exon level.…”

Section: Discussionmentioning

confidence: 99%

“…The majority are benign polymorphisms (SNPs) or variants of unknown significance (VUS) [4,5,23]. Those of pathogenic significance have been described in association with BAP1-TPDS malignancies [4,21,[24][25][26][27][28]. On the other hand, somatic mutations of BAP1 are a frequent event in MM [26,28,29], with a variable rate of occurrence depending on the molecular assay used.…”

Section: Introductionmentioning

confidence: 99%

Mesothelioma families without inheritance of a BAP1 predisposing mutation

et al. 2016

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (n=1), and unknown (n=1). These family units without inheritance of a BAP1 predisposing mutation expand the number of unmutated germline BAP1 families with multiple mesothelioma cases. This suggests that besides the exposure to asbestos other currently unknown genetic or epigenetic factors may be responsible for the high incidence of mesothelioma in BAP1-unmutated families.

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“…Mutations in genes involved in PI3K signaling have been identified in MPM and are thought to contribute to the pathogenesis of MPM (109). Everolimus inhibits PI3K through binding mTOR and is FDA approved for metastatic breast cancer, renal cell carcinoma, subependymal giant cell astrocytoma, GI and lung neuroendocrine tumors, and for prevention of graft failure (110)(111)(112)(113).…”

Section: Pi3k/akt/mtor Pathway Inhibitorsmentioning

confidence: 99%

Novel systemic therapy against malignant pleural mesothelioma

Mancuso

Neal

2017

Transl. Lung Cancer Res.

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Malignant pleural mesothelioma is an aggressive tumor of the pleura with an overall poor prognosis. Even with surgical resection, for which only a subset of patients are eligible, long term disease free survival is rare. Standard first-line systemic treatment consists of a platinum analog, an anti-metabolite, and sometimes anti-angiogenic therapy, but there is currently no well-established standard therapy for refractory or relapsed disease. This review focuses on efforts to develop improved systemic therapy for the treatment of malignant pleural mesothelioma (MPM) including cytotoxic systemic therapy, a variety of tyrosine kinase inhibitors and their downstream effector pathways, pharmacologic targeting of the epigenome, novel approaches to target proteins expressed on mesothelioma cells (such as mesothelin), arginine depletion therapy, and the emerging role of immunotherapy. Overall, these studies demonstrate the challenges of improving systemic therapy for MPM and highlight the need to develop therapeutic strategies to control this disease.

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Targeted Next-Generation Sequencing of Cancer Genes in Advanced Stage Malignant Pleural Mesothelioma: A Retrospective Study

Cited by 140 publications

References 26 publications

KDR Mutation: A High-Frequency Rare Mutation and its Correlation with other Somatic Mutations in Indian Colorectal Cancer Patients

KDR Mutation: A High-Frequency Rare Mutation and its Correlation with other Somatic Mutations in Indian Colorectal Cancer Patients

Mesothelioma families without inheritance of a BAP1 predisposing mutation

Novel systemic therapy against malignant pleural mesothelioma

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