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Judith A Gilbert Department of Molecular Pharmacology and Experimental Therapeutics, Department of Laboratory Medicine and Pathology, Department of Oncology, Oncology Drug Discovery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA

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Laura J Adhikari Department of Molecular Pharmacology and Experimental Therapeutics, Department of Laboratory Medicine and Pathology, Department of Oncology, Oncology Drug Discovery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA

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Ricardo V Lloyd Department of Molecular Pharmacology and Experimental Therapeutics, Department of Laboratory Medicine and Pathology, Department of Oncology, Oncology Drug Discovery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA

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Joseph Rubin Department of Molecular Pharmacology and Experimental Therapeutics, Department of Laboratory Medicine and Pathology, Department of Oncology, Oncology Drug Discovery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA

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Paul Haluska Department of Molecular Pharmacology and Experimental Therapeutics, Department of Laboratory Medicine and Pathology, Department of Oncology, Oncology Drug Discovery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA

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Joan M Carboni Department of Molecular Pharmacology and Experimental Therapeutics, Department of Laboratory Medicine and Pathology, Department of Oncology, Oncology Drug Discovery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA

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Marco M Gottardis Department of Molecular Pharmacology and Experimental Therapeutics, Department of Laboratory Medicine and Pathology, Department of Oncology, Oncology Drug Discovery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA

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Matthew M Ames Department of Molecular Pharmacology and Experimental Therapeutics, Department of Laboratory Medicine and Pathology, Department of Oncology, Oncology Drug Discovery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA

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immunohistochemical staining (intensity score of 3) for the ten molecular markers studied. Hsp90, TGFBR1, IGF1R, and SSTR5 (the strongest staining biomarkers for the largest number of NETs) were expressed in all tumors from 20 cases in which primary and metastatic

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Dermot O'Toole Department of Clinical Medicine and Gastroenterology, Service de Gastroentérologie, Service d'Anatomie Pathologique, INSERM U773, Service de Radiologie, Service d'Oncologie Bichat-Beaujon, St James's Hospital and Trinity College Dublin, James's Street, Dublin 8, Ireland
Department of Clinical Medicine and Gastroenterology, Service de Gastroentérologie, Service d'Anatomie Pathologique, INSERM U773, Service de Radiologie, Service d'Oncologie Bichat-Beaujon, St James's Hospital and Trinity College Dublin, James's Street, Dublin 8, Ireland

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Anne Couvelard Department of Clinical Medicine and Gastroenterology, Service de Gastroentérologie, Service d'Anatomie Pathologique, INSERM U773, Service de Radiologie, Service d'Oncologie Bichat-Beaujon, St James's Hospital and Trinity College Dublin, James's Street, Dublin 8, Ireland
Department of Clinical Medicine and Gastroenterology, Service de Gastroentérologie, Service d'Anatomie Pathologique, INSERM U773, Service de Radiologie, Service d'Oncologie Bichat-Beaujon, St James's Hospital and Trinity College Dublin, James's Street, Dublin 8, Ireland

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Vinciane Rebours Department of Clinical Medicine and Gastroenterology, Service de Gastroentérologie, Service d'Anatomie Pathologique, INSERM U773, Service de Radiologie, Service d'Oncologie Bichat-Beaujon, St James's Hospital and Trinity College Dublin, James's Street, Dublin 8, Ireland

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Magali Zappa Department of Clinical Medicine and Gastroenterology, Service de Gastroentérologie, Service d'Anatomie Pathologique, INSERM U773, Service de Radiologie, Service d'Oncologie Bichat-Beaujon, St James's Hospital and Trinity College Dublin, James's Street, Dublin 8, Ireland

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Olivia Hentic Department of Clinical Medicine and Gastroenterology, Service de Gastroentérologie, Service d'Anatomie Pathologique, INSERM U773, Service de Radiologie, Service d'Oncologie Bichat-Beaujon, St James's Hospital and Trinity College Dublin, James's Street, Dublin 8, Ireland

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Pascal Hammel Department of Clinical Medicine and Gastroenterology, Service de Gastroentérologie, Service d'Anatomie Pathologique, INSERM U773, Service de Radiologie, Service d'Oncologie Bichat-Beaujon, St James's Hospital and Trinity College Dublin, James's Street, Dublin 8, Ireland

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Philippe Levy Department of Clinical Medicine and Gastroenterology, Service de Gastroentérologie, Service d'Anatomie Pathologique, INSERM U773, Service de Radiologie, Service d'Oncologie Bichat-Beaujon, St James's Hospital and Trinity College Dublin, James's Street, Dublin 8, Ireland

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Pierre Bedossa Department of Clinical Medicine and Gastroenterology, Service de Gastroentérologie, Service d'Anatomie Pathologique, INSERM U773, Service de Radiologie, Service d'Oncologie Bichat-Beaujon, St James's Hospital and Trinity College Dublin, James's Street, Dublin 8, Ireland
Department of Clinical Medicine and Gastroenterology, Service de Gastroentérologie, Service d'Anatomie Pathologique, INSERM U773, Service de Radiologie, Service d'Oncologie Bichat-Beaujon, St James's Hospital and Trinity College Dublin, James's Street, Dublin 8, Ireland

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Eric Raymond Department of Clinical Medicine and Gastroenterology, Service de Gastroentérologie, Service d'Anatomie Pathologique, INSERM U773, Service de Radiologie, Service d'Oncologie Bichat-Beaujon, St James's Hospital and Trinity College Dublin, James's Street, Dublin 8, Ireland

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Philippe Ruszniewski Department of Clinical Medicine and Gastroenterology, Service de Gastroentérologie, Service d'Anatomie Pathologique, INSERM U773, Service de Radiologie, Service d'Oncologie Bichat-Beaujon, St James's Hospital and Trinity College Dublin, James's Street, Dublin 8, Ireland

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aggressive GEP-NETs but their influence on therapy is unknown. Several putative molecular markers predicting either sensitivity or resistance to oncological therapeutics have been proposed. The multidrug resistance protein and other ABC transporters have well

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Andreas Venizelos K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Oncology, Haukeland University Hospital, Bergen, Norway

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Hege Elvebakken Department of Oncology, Ålesund Hospital, Møre og Romsdal Hospital Trust, Ålesund, Norway
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway

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Aurel Perren Institute of Pathology, University of Bern, Bern, Switzerland

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Oleksii Nikolaienko K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Oncology, Haukeland University Hospital, Bergen, Norway

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Wei Deng K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Oncology, Haukeland University Hospital, Bergen, Norway

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Inger Marie B Lothe Department of Pathology, Oslo University Hospital, Oslo, Norway

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Anne Couvelard Department of Pathology, Université de Paris, Bichat Hospital, AP-HP, Paris, France

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Geir Olav Hjortland Department of Oncology, Oslo University Hospital, Oslo, Norway

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Anna Sundlöv Departmentt of Oncology, Skåne University Hospital, Lund, Sweden
Department of Medical Radiation Physics, Lund University, Lund, Sweden

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Johanna Svensson Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden

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Harrish Garresori Department of Oncology, Stavanger University Hospital, Stavanger, Norway

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Christian Kersten Department of Research, Hospital of Southern Norway, Kristiansand, Norway

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Eva Hofsli Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
Department of Oncology, St.Olavs Hospital, Trondheim, Norway

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Sönke Detlefsen Department of Pathology, Odense University Hospital, Odense, Denmark
Department of Clinical Medicine, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark

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Merete Krogh Department of Oncology, Odense University Hospital, Odense, Denmark

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Halfdan Sorbye Department of Oncology, Haukeland University Hospital, Bergen, Norway
Department of Clinical Science, University of Bergen, Bergen, Norway

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Stian Knappskog K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Oncology, Haukeland University Hospital, Bergen, Norway

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have associated microsatellite instability (MSI) with improved prognosis ( La Rosa et al. 2012 , Sahnane et al. 2015 ). However, molecular markers for classification, treatment selection and prognosis for HG GEP-NEN are generally lacking. Some

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Esra Karslioglu French Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

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Alyaksandr V Nikitski Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

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Linwah Yip Division of Endocrine Surgery, Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

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Marina N Nikiforova Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

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Yuri E Nikiforov Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

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Sally E Carty Division of Endocrine Surgery, Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

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EIF1AX gene mutations are reported in both benign and malignant thyroid tumors, with unclear outcomes when detected preoperatively. The aim of this study was to determine the features and outcomes of thyroid nodules with various types of mutation identified in cytologic (fine-needle aspiration) samples on preoperative ThyroSeq testing and with surgical outcomes. In this single-institution retrospective study of 31 consecutive patients, 77% were female and nodule size ranged from 1.5 to 9.4 cm with widely varying cytologic and TI-RADS ultrasound categorizations. Among two main mutational hotspots, 55% were located in exon 2 and 45% at the intron 5/exon 6 splice site. On histology, 45% of -positive nodules were cancer/noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) including 19% encapsulated follicular variant papillary thyroid carcinoma, 10% follicular carcinoma, 10% anaplastic carcinoma (ATC), and 7% NIFTP. Almost half (48%) of patients had one or more coexisting mutations, most frequently RAS. The prevalence of cancer/NIFTP was 80% for mutation with coexisting molecular alteration vs 13% with an isolated mutation (P  = 0.0002). Cancer probability was associated with mutation type and was 64% for splice-site mutation and 29% for non-splice mutation (P = 0.075). All 3 nodules with EIF1AX+RAS+TERT+TP53 mutations were ATC. In summary, in this study, all nodules with an isolated non-splice mutation were benign, one-third of those with an isolated splice mutation were cancer, and most nodules with coexisting with RAS or other alterations were malignant. These findings suggest that clinical management decisions for patients with EIF1AX-mutant nodules should consider both the type of mutation and its co-occurrence with other genetic alterations.

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Susan J Hsiao Division of Molecular and Genomic Pathology, Department of Pathology, University of Pittsburgh School of Medicine, 3477 Euler Way, Room 8031, Pittsburgh, Pennsylvania 15213, USA

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Yuri E Nikiforov Division of Molecular and Genomic Pathology, Department of Pathology, University of Pittsburgh School of Medicine, 3477 Euler Way, Room 8031, Pittsburgh, Pennsylvania 15213, USA

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need for molecular markers The diagnosis of thyroid cancer is typically obtained through ultrasound examination and fine-needle aspiration (FNA) biopsy of suspicious nodules. Cytological examination of cells collected by FNA biopsy is the most reliable

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P J Barrett-Lee Cardiff Breast Unit, Velindre NHS Trust, Cardiff CF14 2 TL, UK

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other candidate markers for a way forward. Molecular markers for chemotherapy response At the present time, no single predictive biological marker has become established in routine practice in breast cancer to assess clinical

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Vincenzo Condello Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, Pisa, Italy
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

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Filomena Cetani Endocrine Unit, University Hospital of Pisa, Pisa, Italy

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Maria Denaro Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, Pisa, Italy

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Liborio Torregrossa Division of Surgical Pathology, University Hospital of Pisa, Pisa, Italy

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Elena Pardi Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

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Paolo Piaggi Department of Information Engineering, University of Pisa, Pisa, Italy

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Simona Borsari Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

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Anello Marcello Poma Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, Pisa, Italy

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Lucia Anna Muscarella Fondazione IRCCS Casa Sollievo della Sofferenza Hospital, Laboratory of Oncology, San Giovanni Rotondo (FG), Italy

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Paolo Graziano Fondazione IRCCS Casa Sollievo della Sofferenza Hospital, Unit of Pathology, San Giovanni Rotondo (FG), Italy

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Maria Grazia Chiofalo Fondazione IRCCS G. Pascale, Thyroid and Parathyroid Surgery Unit, Istituto Nazionale Tumori, Naples, Italy

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Andrea Repaci Endocrinology Unit, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy

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Giovanni Tallini Department of Medicine, Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna School of Medicine, Bologna, Italy

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Francesco Boi Department of Medical Sciences and Public Health, Endocrinology Unit, University of Cagliari, Cagliari, Italy

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Gabriele Materazzi Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, Pisa, Italy

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Fulvio Basolo Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, Pisa, Italy

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Claudio Marcocci Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

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( Riker et al. 2008 , Ganepola et al. 2010 , Condello et al. 2019 ). In order to identify molecular markers to apply in the differential diagnosis of parathyroid tumors, with a particular focus on PC progression, we investigated a wide panel of

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Ruth Foley Department of Haematology and Oncology, Institute of Molecular Medicine, St James’ Hospital, James’ St, Dublin 8, Ireland

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Donal Hollywood Department of Haematology and Oncology, Institute of Molecular Medicine, St James’ Hospital, James’ St, Dublin 8, Ireland

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Mark Lawler Department of Haematology and Oncology, Institute of Molecular Medicine, St James’ Hospital, James’ St, Dublin 8, Ireland

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mechanisms, including cross-activation by agents such as IGF-I ( Culig et al. 1994 ). Potential new molecular markers such as hepsin ( Rhodes et al. 2002 ) have been identified. These and other identified and novel genes implicated in the disease

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Bruno Ragazzon Institut Cochin, Inserm, Department of Endocrinology, Université Paris Descartes, CNRS (UMR 8104), 75014 Paris, France
Institut Cochin, Inserm, Department of Endocrinology, Université Paris Descartes, CNRS (UMR 8104), 75014 Paris, France

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Guillaume Assié Institut Cochin, Inserm, Department of Endocrinology, Université Paris Descartes, CNRS (UMR 8104), 75014 Paris, France
Institut Cochin, Inserm, Department of Endocrinology, Université Paris Descartes, CNRS (UMR 8104), 75014 Paris, France
Institut Cochin, Inserm, Department of Endocrinology, Université Paris Descartes, CNRS (UMR 8104), 75014 Paris, France

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Jérôme Bertherat Institut Cochin, Inserm, Department of Endocrinology, Université Paris Descartes, CNRS (UMR 8104), 75014 Paris, France
Institut Cochin, Inserm, Department of Endocrinology, Université Paris Descartes, CNRS (UMR 8104), 75014 Paris, France
Institut Cochin, Inserm, Department of Endocrinology, Université Paris Descartes, CNRS (UMR 8104), 75014 Paris, France

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et al . 1993 , Rainier et al . 1993 , Gicquel et al . 1997 ). Interestingly, it has been previously demonstrated that IGF2 expression could be used as a molecular marker for the diagnosis of ACC ( Gicquel et al . 2001 ). The IGF signaling pathway

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C J Fabian
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B F Kimler
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M S Mayo
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S A Khan
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and/or RPFNA, there is a great deal of interest in supplementing morphologic interpretations with molecular markers ( Fabian et al. 2002 , Ljung et al. 2004 , Gornstein et al. 2004 , Sneige 2004 ). Simple assessment of ploidy has been

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