Hellenic Accreditation System Annex G1/10 to the Certificate No. 350-4 SCOPE of ACCREDITATION of the Clinical Laboratory of "BioAnalytica-GenoΤype" Private Diagnostic Laboratory for Molecular and Cytogenetic Analysis M. S.A. Tested materials/ products Types of test/ Properties to be measured Applied Standards/ Techniques to be used Cytogenetics 1. Peripheral Blood 1. Karyotype /Detection of congenital chromosome abnormalities 2. Bone Marrow, Peripheral Blood , Surgical Biopsy 1. Karyotype /Detection of acquired chromosome abnormalities Cell Cultures, Karyotyping/ Chromosome analysis (ECA General Guidelines and Quality Assurance for Cytogenetics 2012, for Acquired Cytogenetics, 2013 και for Cytogenetic Investigations in Tumours, 2014)* with CytoVision (Applied Imaging) Molecular Genetics 1. Bone Marrow and Peripheral Blood 1. Detection of fusion gene transcripts: BCR/ABL, PML/RaRa Nested RT-PCR with the Invivoscribe kit* in the GeneAmp PCR System 9700 (Applied Biosystems)* or TC-512 (Techne)* 2. Detection of point mutation V617F in JAK 2 gene In house Amplification Refractory Mutation System (ARMS-PCR) in the GeneAmp PCR System 9700 (Applied Biosystems)* or TC-512 (Techne)* 3. Detection of ITD and D835 mutations PCR and restriction endonuclease in FLT3 gene digestion with the Invivoscribe kit* in the GeneAmp PCR System 9700 (Applied Biosystems)* or TC-512 (Techne)* 2. Bone Marrow , Peripheral Page 1 of 2 1. Rearrangements of genomic sequences PCR with the Invivoscribe kit* in the Annex G1/10 to the Certificate ESYD No. 350-4 10.07.2015 Tested materials/ products Blood , Surgical Biopsy Types of test/ Properties to be measured IgH, TCR, IgH/BCL2 Applied Standards/ Techniques to be used GeneAmp PCR System 9700 (Applied Biosystems) or TC-512 (Techne) 2. Quantitative measurement of Real-Time PCR with the Ipsogen kits transcripts: BCR-ABL-p210, BCR-ABL- (BCR-ABL Mbcr, BCR-ABL mbcr, p190, PML/RaRa, TEL-AML1, WT1 PML/RaRa, TEL-AML1, WT1FusionQuant Kits)* in the Light Cycler 2.0 (Roche) and Rotorgene 3. PCR products, plasmids 1. DNA Sequencing Dye terminator cycle sequencing with the CEQ 8000 Genetic Analyzer (Beckman Coulter)* 4. Paraffin-embedded tissues (section), Surgical Biopsy 1. Mutation detection G719S/C/A (exon DNA Pyrosequencing with QIAGEN 18), Gene deletions (exon 19), T790M & kits* in PyroMark Q24 (QIAGEN) S768I (exon 20), L858R & L861Q/R (exon 21) in EGFR gene and in codons 12 and 13 (exon 2) of K-RAS and ΝRAS genes 5. Surgical Biopsy, Cervicovaginal smears 1. Human papillomas virus (HPV) detection and genotyping [49 types: 6, 11, 16, 18, 26, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 56, 58, 59, 61, 62, 64, 66, 67, 68, 69, 70, 71, 72, 73, 74, 81, 82, 83, 84, 85, 86, 87, 89, 97, 101, 102, 103, 106, 150, 151] PCR, hybridisation and DNA microarrays with Genomica kit* in PCR GeneAmp 9700 (ABI) or PCR TC-512 (Techne), Themomixer (Eppendorf) and Clinical Array Reader (Genomica) Molecular Cytogenetics 1. Bone Marrow and Peripheral Blood 1. Detection of sex and autosomal chromosome aneuploidies 2. Bone Marrow, Peripheral Blood, Plasma Cells, Bone Marrow Biopsy 1. Fusion genes/specific translocations [BCR-ABL, ETO(CBFA2T1)AML1(RUNX1 or CBFA2), IgHCCND1(BCL1), IgH-FGFR3(MMSET), IgH-c-maf, IgH-BCL2, API2/MALT1] 3. Peripheral Blood, Bone Marrow, Surgical Biopsy, Plasma Cells, Bone Marrow Biopsy, Formalin Fixed Paraffin Embedded tissue sections. 1. Gene rearrangements/translocations with variant partners [IgH, MLL, RARa, CBFb, ALK, EWSR1, FKHR, CHOP, SYT, ETV6(TEL), FIP1+PDGFRA, CMYC] Fluorescence in situ hybridization with DNA probes of unique or repetitive sequences (ECA General Guidelines and Quality Assurance for Cytogenetics 2012, for Acquired Cytogenetics 2013 και for Cytogenetic Investigations in Tumours 2014)* for localization of nucleic acid sequences in interphase/metaphase cells with the CytoVision (Applied Imaging)* and the Vysis HYBrite (Abbott Diagnostics)* 2. Chromosome deletions/Gene losses [5/5q, 7/7q, 13q14.3, 13q14.3/13q34, 20q12, P53] 4. Surgical Biopsy, Formalin 1. Gene amplification [Her-2 neu Fixed Paraffin Embedded (ΕRΒΒ2), EGFR, N-MYC, 1q21 tissue sections, Bone Marrow 5. Urine 1. Aneuploidies of chromosomes 3, 7,17 and deletion of 9p21 *Reference to the commercial name of a specific analyzer/kit, refers to a specific analytical method and protocol Page 2 of 2 Annex G1/10 to the Certificate ESYD No. 350-4 10.07.2015 Site of assessment: Laboratory permanent premises: 3-5 Ilision str., GR-115 28, Athens, Greece. Approved signatories: V. Alexiadis, S. Ventis, E. Gourgouveli, D. Iakovaki, Ζ . Kosmaidou – Aravidou, P. Konstantoulakis, T. Tranga, G. Bardi. This Scope of Accreditation replaces the previous one dated 21.04.2015. The Accreditation Certificate No. 350-4, to ELOT EN ISO 15189:2012, is valid until 10.05.2019. Athens, July 10, 2015 Ioannis Sitaras Director of the Laboratories Accreditation Division Page 3 of 2 Annex G1/10 to the Certificate ESYD No. 350-4 10.07.2015