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https://www.readbyqxmd.com/read/29755687/clinical-application-of-targeted-next-generation-sequencing-for-colorectal-cancer-patients-a-multicentric-belgian-experience
#1
Nicky D'Haene, Quitterie Fontanges, Nancy De Nève, Oriane Blanchard, Barbara Melendez, Monique Delos, Marie-Françoise Dehou, Calliope Maris, Nathalie Nagy, Emmanuel Rousseau, Josse Vandenhove, André Gilles, Carine De Prez, Laurine Verset, Marie-Paule Van Craynest, Pieter Demetter, Jean-Luc Van Laethem, Isabelle Salmon, Marie Le Mercier
International guidelines made RAS (KRAS and NRAS) status a prerequisite for the use of anti-EGFR agents for metastatic colorectal cancer (CRC) patients. Daily, new data emerges on the theranostic and prognostic role of molecular biomarkers; this is a strong incentive for a validated, sensitive, and broadly available molecular screening test. Next-generation sequencing (NGS) has begun to supplant other technologies for genomic profiling. We report here our 2 years of clinical practice using NGS results to guide therapeutic decisions...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29719410/oncogene-mutational-analysis-in-chinese-gastrointestinal-stromal-tumor-patients
#2
Qiong Chen, Rong Li, Zhi-Gao Zhang, Qiao-Ting Deng, Kun Li, Hao Wang, Xue-Xi Yang, Ying-Song Wu
Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors and exhibit a high frequency of oncogenic KIT or PDGFRA mutations. Tyrosine kinase inhibitors (TKIs) have been mainly used in the treatment of GISTs bearing KIT/PDGFRA mutations. However, other mutation profiles have been found to affect the sensitivity to and effectiveness of TKIs in the treatment of GISTs. Purpose: The aim of the present study was to describe the mutational status of multiple genes in GIST samples and to provide information for finding potential predictive markers of therapeutic targets in Chinese GIST patients...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29696743/coexistence-of-glandular-papilloma-and-sclerosing-pneumocytoma-in-the-bronchiole
#3
Yuko Kitawaki, Fumiyoshi Fujishima, Shinji Taniuchi, Ryoko Saito, Yasuhiro Nakamura, Ryoko Sato, Yayoi Aoyama, Yoshiaki Onodera, Naoko Inoshita, Yasushi Matsuda, Mika Watanabe, Hironobu Sasano
Both glandular papilloma (GP) and sclerosing pneumocytoma (SP) are rare tumors in the lung. We herein report an extremely rare case of coexistence of these two uncommon tumors. The patient was a 40-year-old Japanese woman with no chief complaint. A solitary nodule of the lung was detected using chest computed tomography. The transbronchial biopsy revealed that the tumor histologically corresponded to GP. The patient subsequently underwent partial resection of the right upper lobe. Histological examination of the resected specimens further revealed that the mass contained two different and independent elements and displayed typically histological features of GP and SP...
April 25, 2018: Pathology International
https://www.readbyqxmd.com/read/29682203/mutation-analysis-of-the-egfr-pathway-genes-egfr-ras-pik3ca-braf-and-akt1-in-salivary-gland-adenoid-cystic-carcinoma
#4
Kosuke Saida, Takayuki Murase, Mayuko Ito, Kana Fujii, Hisashi Takino, Ayako Masaki, Daisuke Kawakita, Kei Ijichi, Yuichiro Tada, Kimihide Kusafuka, Yoshiyuki Iida, Tetsuro Onitsuka, Yasushi Yatabe, Nobuhiro Hanai, Yasuhisa Hasegawa, Hitomi Shinomiya, Ken-Ichi Nibu, Kazuo Shimozato, Hiroshi Inagaki
Adenoid cystic carcinoma (AdCC), one of the most common salivary gland carcinomas, usually has a fatal outcome. Epidermal growth factor receptor (EGFR) pathway gene mutations are important in predicting a patient's prognosis and estimating the efficacy of molecular therapy targeting the EGFR pathway. In this study of salivary gland AdCC (SAdCC), we looked for gene mutations in EGFR, RAS family ( KRAS, HRAS, and NRAS ), PIK3CA, BRAF, and AKT1 , using a highly sensitive single-base extension multiplex assay, SNaPshot...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29619072/a-network-pharmacology-approach-to-uncover-the-multiple-mechanisms-of-hedyotis-diffusa-willd-on-colorectal-cancer
#5
Xinkui Liu, Jiarui Wu, Dan Zhang, Kaihuan Wang, Xiaojiao Duan, Xiaomeng Zhang
Background: As one of the most frequently diagnosed cancer diseases globally, colorectal cancer (CRC) remains an important cause of cancer-related death. Although the traditional Chinese herb Hedyotis diffusa Willd. (HDW) has been proven to be effective for treating CRC in clinical practice, its definite mechanisms have not been completely deciphered. Objective: The aim of our research is to systematically explore the multiple mechanisms of HDW on CRC. Methods: This study adopted the network pharmacology approach, which was mainly composed of active component gathering, target prediction, CRC gene collection, network analysis, and gene enrichment analysis...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29589138/mutational-analysis-of-triple-negative-breast-cancers-within-the-international-breast-cancer-study-group-ibcsg-trial-22-00
#6
Elisabetta Munzone, Kathryn P Gray, Caterina Fumagalli, Elena Guerini-Rocco, István Láng, Thomas Ruhstaller, Lorenzo Gianni, Roswitha Kammler, Giuseppe Viale, Angelo Di Leo, Alan S Coates, Richard D Gelber, Meredith M Regan, Aron Goldhirsch, Massimo Barberis, Marco Colleoni
PURPOSE: We investigated the occurrence and the prognostic and predictive relationship of a selected number of somatic mutations in triple-negative breast cancer (TNBC) patients having known clinical outcomes treated within the IBCSG Trial 22-00. METHODS: A matched case-control sampling selected patients enrolled in the IBCSG Trial 22-00 who had TNBC tumors, based on local assessment. Cases had invasive breast cancer recurrence (at local, regional, or distant site) according to the protocol definition...
March 27, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29464061/natural-and-molecular-history-of-prolactinoma-insights-from-a-prlr-mouse-model
#7
Valérie Bernard, Chiara Villa, Aurélie Auguste, Sophie Lamothe, Anne Guillou, Agnès Martin, Sandrine Caburet, Jacques Young, Reiner A Veitia, Nadine Binart
Lactotroph adenoma, also called prolactinoma, is the most common pituitary tumor but little is known about its pathogenesis. Mouse models of prolactinoma can be useful to better understand molecular mechanisms involved in abnormal lactotroph cell proliferation and secretion. We have previously developed a prolactin receptor deficient ( Prlr -/- ) mouse, which develops prolactinoma. The present study aims to explore the natural history of prolactinoma formation in Prlr -/- mice, using hormonal, radiological, histological and molecular analyses to uncover mechanisms involved in lactotroph adenoma development...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416771/menopause-and-adipose-tissue-mir-19a-3p-is-sensitive-to-hormonal-replacement
#8
Reeta Kangas, Cristina Morsiani, Grazia Pizza, Catia Lanzarini, Pauliina Aukee, Jaakko Kaprio, Sarianna Sipilä, Claudio Franceschi, Vuokko Kovanen, Eija K Laakkonen, Miriam Capri
Tissue-specific effects of 17β-estradiol are delivered via both estrogen receptors and microRNAs (miRs). Menopause is known to affect the whole-body fat distribution in women. This investigation aimed at identifying menopause- and hormone replacement therapy (HRT)-associated miR profiles and miR targets in subcutaneous abdominal adipose tissue and serum from the same women. A discovery phase using array technology was performed in 13 women, including monozygotic twin pairs discordant for HRT and premenopausal young controls...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416736/prognostic-and-histogenetic-roles-of-gene-alteration-and-the-expression-of-key-potentially-actionable-targets-in-salivary-duct-carcinomas
#9
Tomotaka Shimura, Yuichiro Tada, Hideaki Hirai, Daisuke Kawakita, Satoshi Kano, Kiyoaki Tsukahara, Akira Shimizu, Soichiro Takase, Yorihisa Imanishi, Hiroyuki Ozawa, Kenji Okami, Yuichiro Sato, Yukiko Sato, Chihiro Fushimi, Hideaki Takahashi, Takuro Okada, Hiroki Sato, Kuninori Otsuka, Yoshihiro Watanabe, Akihiro Sakai, Koji Ebisumoto, Takafumi Togashi, Yushi Ueki, Hisayuki Ota, Mizuo Ando, Shinji Kohsaka, Toyoyuki Hanazawa, Hideaki Chazono, Yoshiyuki Kadokura, Hitome Kobayashi, Toshitaka Nagao
The molecular characteristics of therapeutically-relevant targets and their clinicopathological implications in salivary duct carcinomas (SDCs) are poorly understood. We investigated the gene alterations and the immunoexpression of crucial oncogenic molecules in 151 SDCs. The mutation rates that were identified, in order of frequency, were as follows: TP53 , 68%; PIK3CA , 18%; H-RAS , 16%; BRAF , 4%; and AKT1 , 1.5%. PIK3CA/H-RAS/BRAF mutations were more common in de novo SDC than in SDC ex-pleomorphic adenoma...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29320776/v600e-braf-versus-non-v600e-braf-mutated-lung-adenocarcinomas-cytomorphology-histology-coexistence-of-other-driver-mutations-and-patient-characteristics
#10
COMPARATIVE STUDY
Kevan J Salimian, Roghayeh Fazeli, Gang Zheng, David Ettinger, Zahra Maleki
OBJECTIVES: We analyzed the morphologic features and clinical characteristics of lung adenocarcinomas (ACAs) harboring mutated BRAF. STUDY DESIGN: A review of the histology/cytology of BRAF-mutated lung ACAs was performed at the Johns Hopkins Hospital from January 1, 2013, to January 1, 2015. Patient demographics, clinical history, and ACA morphology were assessed. RESULTS: Thirty-six cases were identified with a median age of 66 years (range 44-87), 58% (21/36) were female, and 94% (34/36) were current or former smokers...
2018: Acta Cytologica
https://www.readbyqxmd.com/read/29316426/clinical-sequencing-defines-the-genomic-landscape-of-metastatic-colorectal-cancer
#11
Rona Yaeger, Walid K Chatila, Marla D Lipsyc, Jaclyn F Hechtman, Andrea Cercek, Francisco Sanchez-Vega, Gowtham Jayakumaran, Sumit Middha, Ahmet Zehir, Mark T A Donoghue, Daoqi You, Agnes Viale, Nancy Kemeny, Neil H Segal, Zsofia K Stadler, Anna M Varghese, Ritika Kundra, Jianjiong Gao, Aijazuddin Syed, David M Hyman, Efsevia Vakiani, Neal Rosen, Barry S Taylor, Marc Ladanyi, Michael F Berger, David B Solit, Jinru Shia, Leonard Saltz, Nikolaus Schultz
Metastatic colorectal cancers (mCRCs) are clinically heterogeneous, but the genomic basis of this variability remains poorly understood. We performed prospective targeted sequencing of 1,134 CRCs. We identified splice alterations in intronic regions of APC and large in-frame deletions in CTNNB1, increasing oncogenic WNT pathway alterations to 96% of CRCs. Right-sided primary site in microsatellite stable mCRC was associated with shorter survival, older age at diagnosis, increased mutations, and enrichment of oncogenic alterations in KRAS, BRAF, PIK3CA, AKT1, RNF43, and SMAD4 compared with left-sided primaries...
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29228562/clinical-mutational-profiling-of-1006-lung-cancers-by-next-generation-sequencing
#12
Peter B Illei, Deborah Belchis, Li-Hui Tseng, Doreen Nguyen, Federico De Marchi, Lisa Haley, Stacy Riel, Katie Beierl, Gang Zheng, Julie R Brahmer, Frederic B Askin, Christopher D Gocke, James R Eshleman, Patrick M Forde, Ming-Tseh Lin
Analysis of lung adenocarcinomas for actionable mutations has become standard of care. Here, we report our experience using next generation sequencing (NGS) to examine AKT1 , BRAF , EGFR , ERBB2 , KRAS , NRAS , and PIK3CA genes in 1006 non-small cell lung cancers in a clinical diagnostic setting. NGS demonstrated high sensitivity. Among 760 mutations detected, the variant allele frequency (VAF) was 2-5% in 33 (4.3%) mutations and 2-10% in 101 (13%) mutations. A single bioinformatics pipeline using Torrent Variant Caller, however, missed a variety of EGFR mutations...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29214440/massarray-based-simultaneous-detection-of-hotspot-somatic-mutations-and-recurrent-fusion-genes-in-papillary-thyroid-carcinoma-the-ptc-ma-assay
#13
Chiara Pesenti, Marina Muzza, Carla Colombo, Maria Carla Proverbio, Claudia Farè, Stefano Ferrero, Monica Miozzo, Laura Fugazzola, Silvia Tabano
PURPOSE: We exploited the MassARRAY (MA) genotyping platform to develop the "PTC-MA assay", which allows the simultaneous detection of 13 hotspot mutations, in the BRAF, KRAS, NRAS, HRAS, TERT, AKT1, PIK3CA, and EIF1AX genes, and six recurrent genetic rearrangements, involving the RET and TRK genes in papillary thyroid cancer (PTC). METHODS: The assay was developed using DNA and cDNA from 12 frozen and 11 formalin-fixed paraffin embedded samples from 23 PTC cases, together with positive and negative controls...
December 6, 2017: Endocrine
https://www.readbyqxmd.com/read/29165888/molecular-pathology-and-thyroid-fna
#14
REVIEW
D N Poller, S Glaysher
This review summarises molecular pathological techniques applicable to thyroid FNA. The molecular pathology of thyroid tumours is now fairly well understood. Molecular methods may be used as a rule-in test for diagnosis of malignancy in thyroid nodules, eg BRAF V600E point mutation, use of a seven-gene mutational panel (BRAF V600E, RAS genes, RET/PTC or PAX8/PPARG rearrangement), or as a comprehensive multigene next-generation sequencing panel, eg ThyroSeq v2. Molecular methods can also be applied as rule-out tests for malignancy in thyroid nodules, eg Afirma or ThyroSeq v2 or as markers of prognosis, eg TERT promoter mutation or other gene mutations including BRAF V600E, TP53 and AKT1, and as tests for newly defined tumour entities such as non-invasive follicular thyroid neoplasm with papillary like nuclei, or as a molecular marker(s) for targeted therapies...
December 2017: Cytopathology: Official Journal of the British Society for Clinical Cytology
https://www.readbyqxmd.com/read/29045518/negative-hyper-selection-of-metastatic-colorectal-cancer-patients-for-anti-egfr-monoclonal-antibodies-the-pressing-case-control-study
#15
MULTICENTER STUDY
C Cremolini, F Morano, R Moretto, R Berenato, E Tamborini, F Perrone, D Rossini, A Gloghini, A Busico, G Zucchelli, C Baratelli, E Tamburini, M Tampellini, E Sensi, G Fucà, C Volpi, M Milione, M Di Maio, G Fontanini, F De Braud, A Falcone, F Pietrantonio
Background: Refining the selection of metastatic colorectal cancer patients candidates for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies beyond RAS and BRAF testing is a challenge of precision oncology. Several uncommon genomic mechanisms of primary resistance, leading to activation of tyrosine kinase receptors other than EGFR or downstream signalling pathways, have been suggested by preclinical and retrospective studies. Patients and methods: We conducted this multicentre, prospective, case-control study to demonstrate the negative predictive impact of a panel of rare genomic alterations [PRESSING (PRimary rESiStance IN RAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-eGfr monoclonal antibodies) panel], including HER2/MET amplifications, ALK/ROS1/NTRK1-3/RET fusions and PIK3CA mutations...
December 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28936923/egfr-pathway-subgroups-in-chilean-colorectal-cancer-patients-detected-by-mutational-and-expression-profiles-associated-to-different-clinicopathological-features
#16
Karin Alvarez, Paulina Orellana, Cynthia Villarroel, Luis Contreras, Hiroshi Kawachi, Maki Kobayashi, Ana Maria Wielandt, Marjorie De la Fuente, Juan Carlos Triviño, Udo Kronberg, Pilar Carvallo, Francisco López-Köstner
Colorectal cancer is a multistep process affecting several signaling pathways including EGFR (epidermal growth factor receptor), a therapeutic target for metastatic disease. Our aim was to characterize the mutational and expression profiles of the EGFR pathway in colorectal tumors and to integrate these results according to five previously defined groups. We screened seven genes for mutations ( KRAS-BRAF-PIK3CA-PIK3R1-AKT1-MAP2K1-PTEN) and six proteins (EGFR-p110α-p85α-PTEN-phosphoAKT-phosphoMEK1) by immunohistochemistry, PTEN deletion, and MSI...
September 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28931215/berberine-could-inhibit-thyroid-carcinoma-cells-by-inducing-mitochondrial-apoptosis-g0-g1-cell-cycle-arrest-and-suppressing-migration-via-pi3k-akt-and-mapk-signaling-pathways
#17
Liang Li, Xingchun Wang, Rampersad Sharvan, Jingyang Gao, Shen Qu
Berberine, an important natural isoquinoline alkaloid from traditional Chinese medicine, is reported to exhibit multiple pharmacological properties, including anti-microbial, anti-diabetes, anti-obesity, anti-inflammatory and anti-carcinogenic activities. Although studies have shown that a wide range of carcinoma cells could be inhibited by berberine, few studies involved thyroid carcinoma. We therefore examined the effect of berberine on papillary thyroid carcinoma (PTC, the most common subtype) and anaplastic thyroid carcinoma (ATC, the most malignant and aggressive subtype)...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28830562/ciliated-muconodular-papillary-tumors-of-the-lung-with-kras-braf-akt1-mutation
#18
Emiko Udo, Bungo Furusato, Kazuko Sakai, Leah M Prentice, Tomonori Tanaka, Yuka Kitamura, Tomoshi Tsuchiya, Naoya Yamasaki, Takeshi Nagayasu, Kazuto Nishio, Junya Fukuoka
BACKGROUND: Ciliated muconodular papillary tumors (CMPTs) are newly recognized rare peripheral lung nodules that are histologically characterized by ciliated columnar, goblet, and basal cells. Although recent studies have shown that CMPTs constitute a neoplastic disease, the complete histogenesis of CMPTs is not fully understood and molecular data are limited. METHODS: We reviewed four cases of CMPT and performed immunohistochemical and genomic analyses to establish CMPT profiles...
August 22, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28698100/adenosquamous-gallbladder-carcinoma-multigene-hotspot-mutational-profiling-reveals-a-monoclonal-origin-of-the-two-components
#19
Francesca Galuppini, Roberta Salmaso, Elisa Valentini, Cristiano Lanza, Isacco Maretto, Donato Nitti, Massimo Rugge, Matteo Fassan
Adenosquamous carcinoma (ASC) of the gallbladder is a rare malignant tumor that is characterized by a coexisting of glandular and squamous components. In a case of ASC, we performed hotspot multigene mutational profiling of 164 hotspot regions of eleven cancer-associated genes (AKT1, APC, BRAF, CTNNB1, KIT, KRAS, NRAS, PDGFRA, PIK3CA, PTEN and TP53) in the two microdissected components. Both tumor phenotypes resulted characterized by a p.E542K point mutation in the PIK3CA gene, whereas adenocarcinoma component revealed also a TP53 Q331* homozygous stop mutation...
August 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28678173/molecular-and-clinicopathological-differences-by-age-at-the-diagnosis-of-colorectal-cancer
#20
Chu-Cheng Chang, Pei-Ching Lin, Chun-Chi Lin, Yuan-Tzu Lan, Hung-Hsin Lin, Chien-Hsing Lin, Shung-Haur Yang, Wen-Yi Liang, Wei-Shone Chen, Jeng-Kai Jiang, Jen-Kou Lin, Shih-Ching Chang
We compared the clinicopathological and molecular profiles between different age groups of sporadic colorectal cancer (CRC) patients (age <50, 56-60, 60-70, 70-80, and >80); 1475 CRC patients were enrolled after excluding 30 individuals with Lynch syndrome. The mutation spectra for APC , TP53 , KRAS , PIK3CA , FBXW7 , BRAF , NRAS , HRAS , TGFbR , Akt1 , and PTEN were analyzed using polymerase chain reaction (PCR), followed by MassArray and microsatellite (MSI-high) analysis by performing genotyping. Male patients (74...
July 5, 2017: International Journal of Molecular Sciences
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