لیست آزمایشهای ژنتیکی خدمات تخصصی برای ارجاع بیماران از سوی پزشکان و متخصصان
کلینیک ژنوتو با بهرهگیری از پیشرفتهترین تکنولوژیهای آزمایشگاهی و تیمی از متخصصان ژنتیک، مجموعهای کامل از آزمایشهای ژنتیکی مرتبط با پیشگیری، تشخیص و درمان هدفمند سرطان را ارائه میدهد.
این صفحه بهطور خاص برای پزشکان، متخصصان، و مراکز درمانی طراحی شده است تا بتوانند با آگاهی کامل، بیماران را جهت بررسی ژنتیکی و دریافت خدمات مشاوره و آزمایش، به کلینیک ژنوتو ارجاع دهند.
Targeted Therapy
| Method | Gene | Description |
|---|---|---|
| HER2/neu Amplification | in Breast Cancer | In breast cancer patients, a FISH test on breast cancer tissue can show whether the cells have extra copies of the HER2/neu gene and therefore more HER2 receptors, which receive signals that stimulate the growth of breast cancer cells. So, patients with extra copies of the gene are more likely to respond to treatment with Trastuzumab (Herceptin), a drug that blocks the ability of HER2 receptors to receive growth signals. |
| ALK Fusion | in NSCLC | ALK FISH assay is a FDA-approved test in guiding therapy with Crizotinib in NSCLC. |
| EGFR Amplification | in NSCLC | The EGFR copy number determined by FISH is one of the biomarkers used to select the correct therapy for NSCLC. Inhibitors of the tyrosine kinase activity of these receptors (e.g. Erlotinib, gefitinib) are suitable in case of gene amplification. |
| ROS1 | in NSCLC | Four FDA-approved drugs have significant activity against ROS1+ NSCLC: Crizotinib, Ciritinib, Lorlatinib, and Entrectinib. |
| Detection of PDGFRB Gene Rearrangement | in MDS/MPD | This FISH test from fresh bone marrow samples of patients with MDS/MPD with a high index of suspicion based on karyotyping showing a 5q31~33 anomaly is indicated as an aid in the selection of MDS/MPD patients for whom Gleevec® (Imatinib Mesylate) treatment is being considered. |
Diagnostic Use
| Method | Gene | Description |
|---|---|---|
| 15-17 translocation | in Acute Promyelocytic Leukemia | A subtype of acute myeloid leukemia called Acute Promyelocytic Leukemia is defined by the translocation between the chromosomes 15 and 17. |
| t(8:21) , AML1-ETO | in AML M2 -M4 | The t(8;21)(q22;q22) is the most commonly observed chromosomal translocation in Acute Myeloid Leukemia (AML) patients; it generates the AML1-ETO (AE) fusion protein. Adult AMLs with AML1-ETO account for approximately 5%–8% and are associated morphologically with AML-M2/M4 subtypes. The median age of these patients is considerably lower, and the prognosis is better compared to normal-karyotype AMLs or other chromosome aberrations. This favorable consequence is associated with a higher complete remission (CR) rate and lower relapse incidence. |
| ETV6-RUNX1 translocation | in ALL | - Genetic alterations in the RUNX1 gene are associated with benign and malignant blood disorders, particularly of Megakaryocyte and Myeloid lineages. - It is known that ETV6-RUNX1 is usually related to favorable prognosis, but MLL aberration has been associated with poor prognosis among pediatric Acute Lymphoblastic Leukemia (ALL). |
| MYC, BCL2 and BCL6 Rearrangements | in Large B-cell Lymphomas | Rarely, B-cell lymphomas show morphologic features similar to those from both or somewhere in between diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL). Many of these may be classified as either high grade B cell lymphoma (HGBCL) with MYC and BCL2 and/or BCL6 rearrangements (Double-hit or Triple-hit lymphomas) or HGBCL, not otherwise specified (NOS). Testing by FISH for MYC, BCL2, and BCL6 rearrangements must be performed on all large B-cell lymphomas to rule out DH/TH lymphomas, and such cytogenetic studies are essential, especially in cases with enlarged but ambiguous cell size. For such cases with morphologic features of both DLBCL and BL, a diagnostic category of HGBCL, NOS should be considered, but because these cases are rare, all other possibilities ought to be ruled out carefully. These 2 entities—HGBCL with MYC and BCL2 and/or BCL6 rearrangements, and HGBCL, NOS—replace the classification of B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL. |
| EWSR1 Rearrangement | in Sarcoma | EWSR1 is located on chromosome 22q12.2 and is exposed to aberrations such as rearrangements due to its multifunctional role. Beyond Ewing Sarcoma, EWSR1 rearrangements occur in various soft tissue and bone lesions. |
Prognostic Use
| Method | Gene | Description |
|---|---|---|
| 11q , 17p, 13q Deletion .p53, t(11:14). t(4:14), t(14:16) | in Multiple Myeloma | Cytogenetic Abnormalities (CAs) are significant predictors for the prognosis of Multiple Myeloma (MM). Certain CAs like t(4;14), t(14;16), t(14;20), gain/amp(1q21), del(1p), and del(17p) are associated with a poor prognosis. |
| Aneuploidy for Chromosomes 3, 7, 17, and Loss of the 9p21 Locus | in Bladder Cancer | It is FDA approved to detect aneuploidy for chromosomes 3, 7, 17, and loss of the 9p21 locus via fluorescence in situ hybridization (FISH) in urine specimens from persons with hematuria suspected of having Bladder Cancer as a screening and prognostic tool. |
FISH method
It employs a fluorescently labeled probe that hybridizes with DNA to detect gene copy number changes (e.g. HER2 amplification) or gene fusions in tumor sections or cells.
| Method | Gene | Description |
|---|---|---|
| Peripheral blood/Bone Marrow Karyotyping | in Myeloid Disorders | Cytogenetic results showed that 30% of patients with myeloid disorders had abnormal karyotypes. |
| Deletion of Chromosome 7 or 20 , 5 and +8 | in MDS | - If a patient with Myelodysplastic Syndrome has a tumor that shows the loss of chromosome 7, it usually progresses quickly. On the other hand, another patient with MDS whose tumor shows the deletion of chromosome 20 typically sees the disease progress more slowly. - According to the Revised International Prognostic Scoring System for Myelodysplastic Syndromes (IPSS-R): “low” risk MDS contains a normal karyotype and isolated loss of Y; “high” risk contains a complex karyotype (≥3 abnormalities), trisomy 8, and abnormalities of chromosome 7; and “intermediate” risk contains all other abnormalities. |
| 13q,11q,17p Deletion, Trisomy12, IGHV | in CLL | Common abnormalities include: - Deletion 13q: associated with a favorable prognosis. - Trisomy 12: associatedwith intermediate prognosis. - Deletion 11q (ATM gene): associated with more aggressive disease - Deletion 17p (TP53 gene): associated with poor prognosis due to resistance to treatment. - Complex Karyotype (CK): Patients with high CK exhibit worse prognosis. - NOTCH1 mutations: Unfavorable prognosis and distinctive gene expression profile. Other factors affecting prognosis include: - Immunoglobulin heavy variable gene (IGHV) status: Mutated IGHV correlates with better outcomes. - ZAP-70 expression: High expression is associated with worse prognosis. - Beta-2 microglobulin levels: Elevated levels indicate poorer prognosis. - Clinical Stage: Early-stage CLL generally has a better prognosis. - Response to treatment: Achieving complete remission improves outcomes . |
Karyotype
It analyzes the number and structure of chromosomes in cells to identify large-scale genetic abnormalities, such as aneuploidies (e.g. trisomy 21) or structural rearrangements (e.g. translocations, deletions, duplications).
Targeted Therapy
| Method | Gene | Description |
|---|---|---|
| EGFR T790M mutation test | in Lung Cancer | Detecting somatic mutations in the EGFR gene from FFPE tumor DNA or plasma ctDNA is used as a companion diagnostics method for the selection of targeted therapies in lung cancer patients. The T790M mutation, also known as Thr790Met, occurs within the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene. In clinical practice, T790M is associated with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in patients with Non-small Cell Lung Cancer (NSCLC). However, irreversible covalent inhibitors like Osimertinib can overcome this resistance. |
| BRAF V600E Mutation | in Melanoma | This PCR assay is used for detection of the BRAF V600E mutation in patients with melanoma, who might be candidates for treatment with Vemurafenib. |
| KRAS AND NRAS mutation | in Metastatic CRC | - Patients with NRAS wild-type CRC benefit from targeted treatment with EGFR inhibitors. - Two commonly used EGFR inhibitors are Cetuximab (Erbitux) and Panitumumab (Vectibix). - Clinical trials have shown that NRAS mutations in specific exons (exons 2, 3, and 4) can predict a lack of clinical benefit from anti-EGFR therapy when combined with chemotherapy in the first-line setting. - Recent developments have led to RAS-targeting drugs, including Lumakras (sotorasib, AMG510), approved for treating KRAS G12C-mutant NSCLC patients. |
| JAK2, MPL,Calreticulin | in Myeloproliferative neoplasms (NPM) | 1. JAK2 (Janus kinase 2): JAK2 is a critical player in MPNs. It's a tyrosine kinase that regulates cell growth and differentiation. The JAK-STAT pathway, which JAK2 is part of, is activated in most MPNs, regardless of the specific driver mutations. - The JAK2 V617F mutation is the most common genetic alteration in MPNs, leading to Uncontrolled Cell Proliferation. - The oral JAK1/JAK2 inhibitor Ruxolitinib is approved by the FDA for the treatment of intermediate and advanced phase myelofibrosis and in certain cases of Polycythemia Vera. 2. MPL (Thrombopoietin Receptor): - MPL is another key player. It's a receptor for thrombopoietin, which regulates platelet production. - Mutations in MPL can drive MPNs, although they are less frequent than JAK2 mutations. - MPL mutations often coexist with JAK2 or CALR mutations. 3. Calreticulin (CALR): - CALR is an endoplasmic reticulum chaperone protein involved in protein folding and quality control. - Mutations in the CALR gene were discovered in 2013 in a subset of JAK2/MPL-negative MPN patients. - These mutations activate the JAK/STAT pathway by binding to MPL, leading to MPN development. - Interestingly, CALR mutations are associated with a decreased risk of Thrombosis in Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) patients |
| KIT D816V Mutation | in Systemic Mastocytosis | This test is used for qualitative detection of the KIT c. 2447A>T (D816V) mutation found in most adults (>80%) with systemic mastocytosis. Detection of the KIT D816V mutation can aid in the diagnosis of systemic mastocytosis and guide the choice of therapy since it is associated with Resistance to Imatinib Mesylate. |
| ESR1 Mutations | in Breast Cancer | ESR1 Mutations and Hormone Therapy Resistance: - ESR1 (Estrogen Receptor 1) mutations are common in metastatic hormone receptor-positive Breast Cancer. - These mutations often arise after treatment with aromatase inhibitors, which are used to deprive cancer cells of estrogen. - The mutations occur in the ligand-binding domain (LBD) of the ESR1 gene. - ESR1 mutations are associated with Shorter Progression-free Survival in endocrine therapy-resistant cancers. |
Prognosis
| Method | Gene | Description |
|---|---|---|
| FLT3 ITD, NPM1 , WT1 mutation | in AML | 1- FLT3-ITD (Internal Tandem Duplication): - FLT3 is a gene that encodes a receptor tyrosine kinase involved in cell growth and differentiation. - FLT3-ITD is a mutation where a portion of the FLT3 gene is duplicated, leading to an abnormal protein. - Patients with FLT3-ITD tend to have higher white blood cell counts and blast counts at diagnosis. - Unfortunately, FLT3-ITD is associated with a poorer prognosis in AML. 2- NPM1 Mutation: - NPM1 (Nucleophosmin 1) is another gene commonly mutated in AML. - NPM1 mutations are generally associated with a better outcome, especially if FLT3-ITD is absent. - When NPM1 mutations co-occur with FLT3-ITD, the impact on prognosis can vary. 3- WT1 Mutation: - WT1 (Wilms tumor 1) is a gene involved in normal kidney development. - In AML, WT1 mutations are independently associated with poorer overall survival. - These mutations are also strongly associated with Minimal Residual Disease (MRD) positivity |
PCR
PCR-based targeted genetic profiling is the most common technology used in cancer diagnostics for both DNA- and RNA-based applications. It is used for the detection of small DNA mutations (e.g., EGFR mutations), gene fusions (e.g., RNA-based testing for ALK), or DNA methylation analysis using methylation-specific PCR (e.g., MGMT promoter methylation in glioblastoma or Septin9 gene methylation in CRC). Many modifications of this basic method are continuously being developed to increase the sensitivity of detecting biomarkers from trace sources.
| Method | Gene | Description |
|---|---|---|
| BCR-ABL fusion | in Chronic Myeloid Leukemia | A 9-21 chromosomal translocation (Philadelphia chromosome) RT-qPCR test is FDA-approved for nilotinib administration in Chronic Myeloid Leukemia |
| Isocitrate dehydrogenase-1 (IDH1) mutation | in Lung Cancer | This biomarker is tested with qualitative real-time PCR to check for oncogenic changes. It is FDA-approved and indicated as an aid in identifying acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients benefiting from treatment with TIBSOVO® (ivosidenib) or in identifying AML patients for treatment with REZLIDHIATM (olutasidenib). |
| PIK3CA | in Breast Cancer | real-time qualitative PCR, is used for the detection of 11 mutations in the PIK3CA gene in FFPE tumor DNA or ctDNA of patients with breast cancer to identify patients for targeted treatment with PIQRAY® (Alpelisib). |
RT-PCR
It detects and quantifies specific RNA sequences by converting them into complementary DNA (cDNA) and amplifying the target using real-time polymerase chain reaction. It is commonly used to assess gene expression levels or detect gene fusions and mutations.
| Method | Gene | Description |
|---|---|---|
| Methylation in the Promoter Region of the SEPT9, NDRG4 or BMP3 | in Colorectal Cancer | Real-time methylation-specific PCR on plasma DNA is used to screen CRC in individuals older than 50 years and that cannot be screened by standard methods. |
METHYLATION ASSAY
It evaluates DNA methylation patterns at specific gene regions to assess epigenetic changes that may affect gene expression. This assay helps identify gene silencing, especially in tumor suppressor genes, and is useful in cancer diagnostics and classification.
| Method | Gene | Description |
|---|---|---|
| NTRK Gene Fusion | in Solid Tumors | Testing of NTRK gene fusion (NGS) is approved in patients with solid tumors for treatment with larotrectinib which is a tumor agnostic drug approved by the FDA and also for pembrolizumab administration in relation to the indication of high tumor mutational burden. |
| Microsatellite instability (MSI) | in Pembrolizumab | Mismatch repair deficiency (dMMR) results in microsatellite instability (MSI) and is strongly associated with responsiveness to programmed death-1 receptor (PD-1)-blocking antibodies. Based on these results, PD-1-blocking antibody pembrolizumab was the first tumour-agnostic treatment to be granted Food and Drug Administration approval based on the presence of MSI as a biomarker. |
| STR Analysis | Bone Marrow Engraftment (BME): - BME helps differentiate between the donor's DNA and the recipient's DNA after a bone marrow transplant. - Initially, samples from both the donor and recipient are required for BME. Subsequent tests only need the recipient's sample1. - White blood cell sub-population BME can also be studied, focusing on B cells, myeloid cells, T cells, and NK cells. | |
| Tumor Mutational Burden (TMB) | Large assays with ~1.1 Mb of coding genome using NGS are needed to accurately assess TMB. Comprehensive Genomic Profiling (CGP) analyzes hundreds of biomarkers simultaneously, including TMB. TMB measured from blood (bTMB) using CGP has been associated with improved clinical outcomes when ≥ 20 mutations per megabase were detected in mNSCLC. - A high level of tumor mutation burden means that you may be a good candidate for anti-PD1 or anti-PD-L1 immunotherapy. These drugs work by boosting the immune system to attack cancer cells. The drugs that target PD-1 or PD-L1 are checkpoint inhibitors. FDA approves Pembrolizumab for adults and children with TMB-H solid tumors. | |
| Homologous Recombination Deficiency Test (HRD) | Homologous recombination deficiency (HRD) is a tumor characteristic that is defined by the inability to accurately repair double-strand breaks (DSBs) in DNA via homologous recombination. HRD can be assessed via 2 different types of biomarkers. In ovarian and Breast cancers, these include individual mutations in breast cancer susceptibility genes 1 or 2 (BRCA1 or BRCA2) and the assessment of genomic instability. Genomic instability, or large-scale structural rearrangements to chromosomes, results in specific measurable genomic aberrations and serves as the “collateral damage” that can occur to the genome as a result of HRD. |
NGS Hereditary cancers panel
Some types of cancer are more likely to be hereditary. Therefore, Inherited mutations have been linked to susceptibility to many different types of cancers.
So Geneoto has designed a comprehensive test for all hereditary cancers according to Whole Exome Sequencing method. Also, Geneoto offers targeted tests for detection of special cancer syndromes like HBOC, Lynch, MENI/II, Cowden, Peutz-Jeghers Syndromes and so on. Below is a list of common cancers, and the most common gene panels that have been linked to increased risk for each.
GENEOTO Heredity Test
This is a comprehensive test with proper depth for detection of mutations in susceptibility genes of all cancer types. Including:
-
ABCB1
ABCC2
ABL1
ABL2
ACD
ACVR1B
ACVR2A
ADA
AIP
AJUBA
AKT1
AKT2
AKT3
ALK
AMG
ANKRD26
APC
AR
ARHGAP35
ARID1A
ARID5B
ARL11
AS1
ASXL1
ATM
ATR
ATRX
AURKB
AXIN2
B4GALT3
BABAM1
BAP1
BARD1
BLM
BMPR1A
BRAF
BRCA1
BRCA2
BRIP1
BUB1
BUB1B
BUB3
CASP10
CASP8
CASR
CBFB
CBL
CCDC170
CCNB1
CCND1
CCNE1
CD9
CDA
CDC73
CDH1
CDK12
CDK4
CDKN1A
CDKN1B
CDKN1C
CDKN2A
CDKN2B
CDKN2C
CEBPA
CEP57
CFTR
CHD7
CHEK2
CHIC2
CLN
CREBBP
CRIPAK
CRLF2
CSF1R
CTCF
CTNNA1
CTNNB1
CTR9
CYLD
CYP11A1
CYP17A1
CYP19A1
CYP1B1
CYP2A6
CYP2B6
CYP2C19
CYP2C9
CYP26
DAPK1
DDB2
DDR1
DDR2
DDX3X
DICER1
DIS3L2
DNMT3A
DPYD
EGFR
EGR3
EIF4A2
ELAC2
ELF3
ENG
EP300
EPCAM
EPHA3
EPHB2
EPHB6
EPPK1
ERBB2
ERBB3
ERBB4
ERCC2
ERCC3
ERCC4
ERCC5
ERCC6
RG
ESR1
ESR2
EXT1
EXT2
EZH2
FAM175A
FANCA
FANCB
FANCC
FANCD2
FANCE
FANCF
FANCG
FANCI
FANCL
FANCM
FAS
FASLG
FBXW7
FGF10
FGFR1
FGFR2
FGFR3
FGFR4
FH
FHIT
FLCN
FLT1
FLT3
FLT4
FOXA1
FOXA2
FSTL5
GALNT12
GATA2
GATA3
GEN1
GHSR
GNA11
GNAQ
GNAS
GPC3
GREM1
GSTP1
H19
H3F3A
H3F3C
HFE
HGF
HIST1H1C
HIST1H2BD
HNF1A
HOXB13
HRAS
IDH1
IDH2
IGF2
IKZF1
IL2RA
IL2RB
IL2RG
IL7R
INHBA
INPP4B
JAK1
JAK2
JAK3
KCNQ1
KCNQ1OT1
KDM5A
KDM5B
KDM5C
KDM6A
KDR
KEAP1
KIAA1919
KIF1BKIT
KMT2B
KMT2C
KMT2D
KRAS
LAMA2
LCK
LEPR
LIFR
LRRK2
LTK
MALAT1
MAP2K1
MAP2K2
MAP2K4
MAP3K1
MAPK1
MAPK8IP1
MAX
MC1R
MCAT
MECOM
MED13
MEN1
MET
MIR142
MITF
MLH1
MLH3
MLL
MPL
MRE11
MRE11A
MSH2
MSH3
MSH6
MST1R
MSX1
MTHFR
MTOR
MUTYH
MYCMYD88
NAV3
NBN
NCOR1
NELL2
NF1
NF2
NFE2L2
NFE2L3
NOD2
NOTCH1
NOTCH2
NPM1
NQO1
NRAS
NSD1
NTHL1
NTRK1
PALB2
PALLD
PARK2
PARP1
PAX5
PBRM1
PCBP1
PDGFRA
PDGFRB
PHF6
PHOX2B
PIK3CA
PIK3CG
PIK3R1
PINK1
PMS1
PMS2
POLD1
POLE
POLH
POLQ
POT1
POU6F2
PPP2R1A
PRF1
PRKAR1A
PRSS1
PRX
PSMB1
PSMB2
PSMB5
PSMD1
PSMD2
PTCH1
PTEN
PTPN11
PTPRC
RAD21
RAD50
RAD51
RAD51B
RAD51C
RAD51D
RAF1
RAG1
RAG2
RARA
RARB
RARG
RASAL1
RB1
RB1CC1
RECQL
RECQL4
RET
RGS16
RGS8
RGSL1
RHBDF2
RHOBTB2
RNASEL
ROS1
RPL11
RPL22
RPL35A
RPL5
RPS10
RPS17
RPS19
RPS20
RPS24
RPS26
RPS6KB1
RPS7
RUNX1
RXRA
RXRB
RXRG
SBDS
SCG5/GREM1
SDHA
SDHAF2
SDHB
SDHC
SDHD
SEMA4A
SETBP1
SETD2
SF3B1
SH2D1A
SHH
SHOC2
SIN3A
SLC22A1
SLC22A2
SLC31A1
SLC34A2
SLC45A3
SLCO1B1
SLX4
SMAD2
SMAD4
SMAD9
SMARCA4
SMARCB1
SMARCE1
SMC1A
SMC3
SMO
SMYD3
SNCAIP
SOS1
SOX17
SOX9
SPINK1
SPOP
SPRED1
SRC
SRD5A2
SRP72
STAG2
STK11
SUFU
SULT1E1
TAF1
TAS2R38
TBL1XR1
TBX3
TERC
TERF2IP
TERT
TET2
TGFBR1
TGFBR2
TLR4
TMEM127
TNFRSF13B
TOPBP1
TP53
TRRAP
TSC1
TSC2
TSHZ2
TSHZ3
TWIST1
TYK2
U2AF1
UBE2T
UGT1A1
UIMC1
USP9X
VEZF1
VHL
WAS
WRN
WT1
XPA
XPC
XRCC2
XRCC3
YAP1
YES1
ZMYM3
ZNF217
| Method | Description |
|---|---|
| Hereditary Breast and Ovary Cancer syndrome (HBOC Syn.) | ATM, BARD1, BRCA1, BRCA2, CHEK2, CDH1, NF1, PALB2, PTEN, RAD51C, RAD51D, STK11, TP53 |
| Adenomatosis Familial Polyposis and Lynch Syndrome | APC, BMPR1A, EPCAM, MLH1, MSH2, MSH6, PMS2, CHEK2, POLE, PTEN, SMAD4, STK11, TP53, MUTYH |
| Peutz Jeghers Syndrome oSTK11 Cowden Syndrome | STK11 |
| Cowden Syndrome | PTEN |
| Fallopian tube, ovarian, primary peritoneal cancer | ATM, BRCA1, BRCA2, BRIP1, EPCAM, MLH1, MSH2,MSH6, PALB2, PMS2, RAD51C, RAD51D |
| Gastric cancer | APC, CDH1, STK11, EPCAM, MLH1, MSH2, MSH6 |
| Melanoma | BAP1 (especially uveal melanoma), BRCA2 CDK4, CDKN2A, PTEN, TP53 |
| Pancreatic cancer | ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, STK11, TP53 |
| Prostate cancer | ATM, BRCA1, BRCA2, CHEK2, HOXB13, EPCAM, MLH1, MSH2, MSH6, PMS2 |
NGS
NGS is finding application in genetic screening of both germline variants and somatic mutations, including SNVs, indels, and CNAs. It is also being used for RNA-based biomarkers, such as gene fusions and RNA sequencing. The approaches include both amplicon-based screening using primer panels to amplify regions of interest harboring driver gene mutations, or targeted capture and hybridization for selecting fragments of interest for sequencing using capture probes. Different kinds of NGS gene panels have been developed: cancer-specific panels (e.g., for lung cancer, CRC, and breast cancer), general pan-cancer panels for solid tumors or hematological cancers, or panels designed to detect genomic changes for targeted therapies.
In recent years, next-generation sequencing (NGS) has been proven to be one of the most powerful diagnostic tools for rare Mendelian disorders, especially genetically heterogeneous conditions. There are currently two general approaches in the clinical application of NGS assays. When a specific phenotype associated with a number of genes is suspected, targeted gene panel sequencing is applied, whereas exome sequencing (ES) is commonly implemented in the diagnostic evaluation of patients with a wide range of differential diagnoses or uncharacterized genetic diseases.
Pharmacogenomics
Pharmacogenomics is the use of genomic and other “omic” information to individualize drug selection and drug use to avoid adverse drug reactions and to maximize drug efficacy.
The science underlying pharmacogenomics has evolved rapidly over the 50 years since it was first suggested that genetics might influence drug response phenotypes. That process has occurred in parallel with advances in DNA sequencing and other molecular technologies, with striking increases in our understanding of the human genome. There are now many validated examples of the clinical utility of pharmacogenomics, and this type of clinical genomic information is increasingly being generated in clinical laboratories, incorporated into electronic health records, and used to “tailor” or individualize drug therapy.
Pharmacogenomics GeneOto Heal TEST
The GeneotoHeal test is Geneoto comprehensive personalized assay for drug response. It is an advanced NGS based test which defines how the genetic makeup of a patient affects his/her response to drugs. We sequence more than 500 genes which are related to more than 60 FDA approved medicines.
Geneoto EndoPredict Test (mamo nivap)
• The Mamo Nivap assay analyses 12 genes in people newly diagnosed with early-stage, estrogen-receptor-positive, HER2-negative breast cancer.
• It provides a risk score for recurrence to decide if chemotherapy is needed or not.
• It includes the size of the tumor and the lymph node status in risk score calculation.
• The test result are given as an EPclin Risk Score, a number between 1.1 and 6.2.
– An EPclin Risk Score higher than 3.3287 (higher than a 10% risk of recurrence) is interpreted as the cancer having a high risk of recurrence
– An EPclin Risk Score lower than 3.3287 (lower than a 10% risk of recurrence) is interpreted as the cancer having a low risk of recurrence
| Method | Description |
|---|---|
| MammaPrint | A microarray-based prognostic test, uses a 70-gene expression profile from FFPE tissue to predict early-stage breast cancer patients with a high/low risk of recurrence. |
| Oncotype DX | This 21 gene breast cancer signature helps determine the benefit of using chemotherapy in addition to hormone therapy to treat some estrogen receptor-positive, HER2-negative early breast cancers and calculates the Recurrence Score from 0-100 In patients over 50 years old: -A score between 0 and 25 means you have a low risk of the cancer returning if you get hormone treatment. With this score you probably will not benefit from receiving chemotherapy. -A score between 26 and 100 means you have a higher risk that the disease might come back. Both hormone treatment and chemotherapy are likely to be recommended. In patients who are age 50 or younger: -A score of 15 or smaller means you have a low risk of the cancer returning if you get hormone treatment. You probably will not benefit from receiving chemotherapy. -A score between 16 and 20 means you have a low to medium risk of the cancer returning if you get hormone treatment. There may be a small benefit of receiving chemotherapy, but the benefits may not outweigh the risks of side effects. -A score between 21 and 25 means you have a medium risk of the cancer returning if you get hormone treatment. The benefits of chemotherapy may outweigh the risk of side effects. -A score between 26 and 100 means you have a higher risk that the disease might come back. Both hormone treatment and chemotherapy are likely to be recommended. |
| Cologuard and CRC | Cologuard® is a stool DNA-based colorectal cancer screening NGS test for average-risk individuals who are 45 or older. Cologuard uses a biomarker panel which analyzes a person’s stool sample for 10 DNA markers, as well as blood in the stool (hemoglobin). |
Signatures
They are used to study differentially expressed genes in tumor samples and to classify tumors into molecular subtypes, both of which can be predictive of prognosis or treatment response.
Geneoto CTC Enumeration test (MOBID)
– CTC enumeration involves counting the number of circulating tumor cells (CTCs) in a blood sample. High CTC counts are often associated with poor prognosis and can indicate disease progression or recurrence.
– Since the early clinical applications of CTC enumeration, tremendous progresses have been made in three areas:
1) prognostic evaluation and risk estimation for metastatic relapse
2) therapeutic outcome assessment and medication guidance for oncology precision medicine
3) dynamic marker monitoring during the treatment.
– MOBID is a microfluidic based test which is designed by the scientists of Motamed Cancer Institute for valid CTC enumeration in Breast Cancer Patients. The validity of the test is being studied for other cancers in Motamed Cancer Institute.
| Method | Description |
|---|---|
| CTC Characterization Test | - CTC characterization goes beyond counting to analyze the molecular and genetic features of the CTCs. This can include: - Genetic Mutations: Identifying specific mutations that may drive cancer progression. - Gene Expression Profiles: Understanding which genes are active in the CTCs. - Protein Markers: Detecting proteins that are characteristic of tumor cells. - Clinical Applications - Monitoring Treatment Response: Changes in CTC counts and characteristics can indicate how well a patient is responding to treatment. - Early Detection of Metastasis: CTCs can be detected before metastases are visible on imaging, allowing for earlier intervention. - Personalized Medicine: Detailed characterization of CTCs can guide the selection of targeted therapies |
Geneoto cfDNA test
– Circulating free DNA (cfDNA), also known as cell-free DNA, consists of small DNA fragments that are released into body fluids such as blood plasma, urine, and cerebrospinal fluid.
– cfDNA can be used as a biomarker for detecting and monitoring cancer. Elevated levels of cfDNA are often found in cancer patients, and analyzing these fragments can provide insights into tumor genetics and treatment response and help with choosing targeted therapies.
Circulating Tumor Cells (CTC) Enumeration and Characterization
CTC enumeration and characterization are crucial processes in cancer research and treatment. Circulating tumor cells (CTCs) are tumor cells that shed from the primary tumor and intravasate into the peripheral blood circulation system responsible for metastasis. Sensitive detection of CTCs from clinical samples can serve as an effective tool in cancer diagnosis and prognosis through liquid biopsy.
| Method | Description |
|---|---|
| Myeloid lineage markers (Panel 1) | CD11b, CD11c, CD13, CD14, CD15,CD16, CD33, CD64, CD65, MPO |
| Lymphoid lineage markers (Panel 2) | CD2, CD3, CD4, CD5, CD7, CD8, CD19, CD20, CD21, CD22, CD23, CD79a, CD79b, CD200, Kappa, Lambda, sIgM, FMC-7, CD10, CD25, CD103, CD11c, CD45, HLA-DR |
| Leukemia/lymphoma general phenotype screen | CD10, CD18, CD34, CD38, CD45, CD117, TdT, HLA- DR |
| AML-M0 | CD13, CD33, CD38, CD64, CD11b, CD2, CD7, CD19, CD34, CD117, CD45, HLA- DR, TdT, MPO |
| AMI—M1 | CD13, CD33, CD117, CD34, CD38, HLA- DR, MPO, CD45 |
| AML-M2 | CD13, CD33, CD15, CD117, CD34, CD64, HLA- DR, MPO, CD45 |
| AML-M3 | CD13, CD33, CD34, CD2, CD9, CD56, CD64, CD117, CD11b, CD11c, HLA-DR, CD45 |
| AML-M4/M5 | Panel 1 plus CD36, CD68 |
| AML-M6 (Erythroleukemia) | Panel 1 plus CD45, CD71, Glycophorin A |
| AML-M7 (Megakaryoblastic leukemia) | Panel 1 plus CD41, CD42. CD61 |
| CML (Chronic myeloid leukemia) | CD13, CD33, CD64, CD117, CD34, CD45 |
| CMML(Chronic myelomonocytic leukemia) | CD13, CD33, CD14, CD64, CD68, CD45 |
| B-ALL (B cell Acute lymphoblastic leukemia/ lymphoma) | TdT, CD34, CD22, CD79a, CD19, CD20, CD10, CD38, CD45, HLA-DR, Cyto-CD22, Cyto-CD79a |
| T-ALL (T-cell Acute lymphoblastic leukemia/ lymphoma) | CD1a, CD2, CD3, CD4, CD5, CD7, CD8, CD25, CD34, CD45, TdT |
| MM (Multiple myeloma) | CD38, CD138, CD45, CD10, CD19, CD20, CD56, CD117, Kappa, Lambda |
| HCL (Hairy cell leukemia) | CD19, CD20, CD25, CD103, CD11c, CD45, CD123, FMC-7, HLA-DR |
| PNH Panel | Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare blood disorder characterized by chronic intravascular hemolysis, thromboses in unusual sites and cytopenias related to bone marrow failure. The diagnosis is based on the Flow Cytometric (FCM) detection of peripheral blood cell clones lacking the surface molecules linked to the GPI anchor, which is altered by mutations. The pathogenic mechanism of PNH resides in the faulty synthesis of the cell membrane protein anchor Glycosyl-Phosphatidyl Inositol (GPI) due to mutations occurring in the PIG-A gene located on chromosome X |
| Platelet CD markers | CD41, CD41b, CD42, CD42b, CD61,CD71 |
| Acute Leukemia T-Lineage Markers | - TdT-CD1a-CD2-CD3-CD4-CD8- CD5-CD7-CD34-CD16-CD56 - TdT-CD19-CD20-CD10-CD22-IgM- CD79a-CD34-HLA DR |
| Acute Leukemia B-Lineage Markers /Myeloid Markers | MPO-CD13-CD33-CD15-CD14- CD34-CD64-CD117-CD123-HLA DR |
| Chronic Leukemia/Lymphoma T-Lineage Markers / B-Lineage Markers | - CD2-CD3-CD5-CD7-CD4-CD8-CD16-CD56 - CD19-CD20-CD10-CD34-CD5-CD22-CD23-CD25 - CD103-CD38-CD138-HLA-DR-Kap-pa-Lambda-FMC7 |
| HSC Absolute Count Panel | CD34 - CD45 - AAD7 - Microbeads |
| ADAMTS13 (activity- Ab) | Timely determination of plasma ADAMTS-13 activity is essential to discriminatethrombotic thrombocytopenic purpura (TTP) from other types of thrombotic microangiopathy (TMA) with respect to adequate treatment. The generation of monoclonal antibodies (mAbs) that specifically recognize the ADAMTS-13 cleavage site (for von Willebrand factor) is a method for determination of plasma ADAMTS-13 activity. |
| Immunodeficiency Panel | - CD3-CD4-CD8 - CD19-CD20 - BCD16-CD56 |
| Leukocyte Adhesion Deficiency Panel | CD3-CD19 CD18-CD11a CD18-CD11b |
| Chromosomal Breakage Test : Fanconi Anemia | - A sample of peripheral blood lymphocytes is collected from the patient. - These cells are exposed to DEB or MMC, which induce DNA damage. - The laboratory then examines the chromosomes in these cells to detect any breaks or abnormalities. - Increased chromosomal breakage is a characteristic feature of FA. - This test is highly specific and considered diagnostic for FA |
Flow Cytometry
It is often applied in leukemia and lymphoma diagnostics to identify and count cells by using a panel of fluorescently labeled antibodies. It is also deployed to quantitate DNA in cancer cells by treating them with DNA-binding, light-sensitive dyes. Changes in DNA quantity indicate cancer recurrence in breast, prostate, or bladder cancer. What is more, it has application in CTC-based biomarkers, as well.
It is multi-parametric. It also allows analysis at single cell level (benefit over IHC in a number of liquid cancers including hairy cell leukemia).
Detection of hairy cell leukemia can be easily accomplished by using BRAF V600E mutation specific antibody.
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