Our laboratory performs the whole range of molecular tests required by modern medicine to identify the mutation and thus find the most appropriate treatment for the patient.
Mutations
A mutation is any change in the sequence of nucleotides in the DNA chain.
Mutations are divided into small-scale and large-scale/recombination mutations.
Small-scale mutations involve one nucleotide (point mutation) or a few nucleotides and include the phenomena of substitution of one nucleotide for another, deletion where one or a few nucleotides are removed from the DNA and insertion where one or a few nucleotides are added to the DNA.
Large-scale mutations involve broad changes in chromosomal structure and include gene amplifications or duplications, chromosomal inversions where a reversal of the orientation of a chromosome segment occurs, chromosomal shuttling where an exchange of genetic material between non-homologous chromosomes occurs, and large-scale deletions or insertions of nucleotides.
Methylation
DNA methylation is an epigenetic mechanism whereby methyl groups are added to the cytosines in DNA resulting in chromatin compaction and suppression of gene expression. In cancer cells, hypermethylation of promoters of tumour suppressor genes is most commonly observed, resulting in their inactivation.
Gametic and Somatic Mutations
Gametic mutations have the potential to be inherited, as the mutation occurs in either the egg or the sperm cell.
Somatic mutations are not inherited and are not found in germ cells and arise sporadically in the population.
Molecular pathology recommends the use of molecular techniques and markers to study diseases.
In histopathology, the study of molecular markers complements the information provided by the histological examination and is used to personalise the treatment that will be followed by the patient.
In general, the study of molecular markers serves three purposes, diagnosis, prognosis, and prediction, with several markers, however, overlapping and contributing to more than one category.
1) They refer to indicators that assist in diagnosis
2) Used to provide and obtain additional information that will contribute to a more accurate diagnosis.
3) An increasing number of diagnoses are being exclusively defined by the World Health Organization (WHO) on the basis of their molecular profile.
4) Some markers help to identify underlying familial syndromes.
These markers provide additional information on the aggressiveness of the tumour and thus on the patient's prognosis.
In order to be useful, they must provide additional prognostic information beyond that provided by immunohistochemical staining.
In some cases, the detection of a prognostic factor may influence the oncologist's decision whether to give the patient additional chemotherapy.
For example, in patients with breast cancer, the detection of a high risk of recurrence in Oncotype Dx will usually prompt the oncologist to offer the patient adjuvant chemotherapy.
Predictive markers basically predict which treatments the tumour will respond to.
Markers that predict response to targeted therapy.
By targeting specific molecular changes in tumour cells, these therapies have a strong effect on neoplastic cells without affecting normal cells.
The treatment includes:
1) Tyrosine kinase inhibitors
2) Serine/threonine kinase inhibitors
3) GTPase inhibitors
4) Monoclonal antibodies
5) Inhibitors of DNA repair mechanisms (e.g., PARP inhibitors)
Treatment with these drugs helps to keep the cancer under control and prevent further progression rather than cure it.
However, the cancer gradually develops resistance to treatment (usually 1 to 2 years after initiation):
1) They may develop secondary mutations in the same gene that is targeted
2) May develop other changes in the gene targeted (e.g., amplification)
3) May develop molecular changes in pathways that bypass the targeted gene.
Markers predicting response to immunotherapy
Treatment with immunotherapeutic agents manipulates the immune system to target tumour cells.
Immune checkpoints are molecules expressed by immune cells that moderate the immune response.
Immune checkpoint inhibitors (ICIs) are a type of immunotherapy that blocks the function of immune checkpoints. As a result, tumour cells cannot suppress the immune response against the tumour and the immune system targets the neoplastic cells.
ICIs help to keep the neoplasm under control but increasing reports in the literature also report positive effects in the treatment of metastatic cancer.
Some markers that help predict response to immunotherapy include:
1) PDL-1 expression testing using immunohistochemistry (e.g., non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma, urothelial carcinoma, triple negative breast cancer, esophageal cancer)
2) The control of DNA repair and maintenance mechanism (MMR) protein damage as seen in colorectal cancer, endometrial cancer, upper gastrointestinal cancers and pancreaticobiliary cancers.
3) The measurement of tumor mutation burden (TMB) which refers to the count of the number of mutations carried by cancer cells.
Molecular Testing
Colorectal cancer:
Microsatellite instability analysis (MSI)
2) KRAS mutations
3) NRAS mutations
4) BRAF mutations
5) Colorectal cancer predisposition panel
Colon and colorectal non-polyposis cancer (HNPCC)- Lynch syndrome
Microsatellite instability analysis (MSI)
Analysis of DNA repair mechanism proteins MMR
3) BRAF V600E/K
4) Lynch syndrome panel
Familial adenomatous polyposis (FAP)
1) APC
2) Multipathology syndrome predisposition panel
Breast/ovarian cancer (high-grade)
1) biomarker enhancement HER-2
2) BRCA1/2 - inherited mutations
3) BRCA1/2 - MLPA (deficiencies/duplications)
4) BRCA1/2 inherited mutations and MLPA (deficiencies/proliferations)
5) BRCA1/2 somatic mutations
6) Breast/ovarian cancer predisposition panel
Cervical cancer
HPV detection and typing
Thyroid cancer
1. BRAF V600E/K
2. RET (MEN2)
Parathyroid cancer
Head/neck cancer
EGFR (gene amplification)(7p12)
Atypical lipomatous tumour/well-differentiated liposarcoma
MDM2 (12q14-q15) gene amplification
Non-small cell lung cancer
1) EGFR mutation
2) BRAF V600E/K
3) KRAS mutation
4) ALK rearrangements
5) ROS1 rearrangements
6) RET rearrangements
7) NTRK fusion
8) PD-L1 expression
9) PIK3CA-5 mutations
10) PIK3CA-11 mutations
12) MET gene amplification
13) FGFR1 gene amplification
Melanoma
1) BRAF V600E/K
2) BRAF (all exons)
3) NRAS (exons 2,3,4)
4) Malignant melanoma predisposition panel
Gastrointestinal stromal tumours (GIST)
1) KIT mutation
2) PDGFRA mutation
Urothelial carcinoma
1)PD-L1 expression
Gastric adenocarcinoma
1) biomarker amplification HER-2/neu
2) Gastric cancer predisposition panel
Pancreatic cancer
Pancreatic cancer predisposition panel
ALK
What it is: The ALK gene encodes a receptor for tyrosine kinase on the cell surface. Binding to the receptor activates the RAF, RAS and MEK signaling pathways.
The result of this signaling is cell growth and cell proliferation.
Transpositions of ALK that bring it into conjugation with other genes (e.g., ALK-EML4) lead to overexpression of ALK as part of the chimeric protein.
Why the test is done: In non-small cell lung cancer, the presence of ALK translocation predicts sensitivity to tyrosine kinase inhibitors (TKIs) (e.g., Crizotinib, Ceritinib, Alectinib)
Frequency: Approximately 2% of non-small cell lung carcinomas.
More common in mucinous lung adenocarcinomas.
More common in non-smokers.
Less common in squamous cell carcinomas of the lung.
FGFR1
What it is: The FGFR1 gene encodes a receptor for tyrosine kinase on the cell surface. Binding to the receptor activates the RAF, RAS and MEK signaling pathways
The result of this signaling is cell growth and cell proliferation.
The result of this signaling is cell growth and cell proliferation.
FGFR1 gene amplifications are the second most frequent mutations in non-small cell lung cancer after EGFR mutations and are even more frequent than ALK, ROS1 and RET transpositions.
Why the test is done: In non-small cell lung cancer, the detection of gene amplification of the FGFR1 gene is one of the most important biomarkers for the treatment of lung cancer.
Frequency: FGFR1 gene amplification is found in 20% of squamous cell lung cancer carcinomas.
APC
What it is: The APC gene encodes the APC protein which has a dominant role in a variety of cellular processes. It has a tumor suppressive effect preventing uncontrolled cell proliferation.
Why the test is done: The test is done to check for the existence of a syndrome known as Familial Adenomatous Polyposis which increases the risk of colorectal cancer and is inherited in an autosomal dominant manner. This syndrome does not affect patients with APC I1307K mutation.
Frequency: The proportion of individuals with Familial Adenomatous Polyposis ranges from 1 in 22,000 to 1 in 7,000, and a proportion of patients, about 30%, have no family history of the disease and are the first to develop the mutation.
BRAF
What it is: The BRAF gene encodes the B-Raf protein which is involved with several tyrosine kinase receptors. Its activation results in cell growth and cell proliferation.
The most common genetic mutation of the kinase involves V600E.
Why the test is done:
Melanoma: Detection of the BRAF V600E mutation predicts the sensitivity of the neoplasm to BRAF and MEK inhibitors.
ΜΜΚΠ: Detection of the BRAF V600E mutation predicts the sensitivity of the neoplasm to BRAF and MEK inhibitors.
Colorectal cancer: Detection of BRAF V600E mutation predicts sensitivity to the combination of BRAF inhibitor with EGFR inhibitor.
Thyroid cancer:
1. The presence of BRAF V600E mutation in papillary thyroid carcinoma is associated with a more aggressive course of the carcinoma.
2. In anaplastic thyroid carcinoma the presence of BRAF V600E mutation predicts sensitivity to response to BRAF (dabrafenib) and MEK (trametinib) inhibitors.
3. The presence of a mutation in BRAF V600E cofactors in favor of papillary thyroid cancer over other subtypes.
Frequency:
Melanoma: Approximately 50% of melanomas have a BRAF mutation, most commonly due to exposure to solar radiation.
ΜΜΚΠ: Less than 5% of cases. Probably more common in non-smokers and in adenocarcinomas with a microfollicular growth pattern.
Colorectal cancer: Occurs in about 10% of cases. It shares similar clinicopathological features with colorectal tumours with deficiency of mismatch base repair (dMMR) mechanisms.
Thyroid cancer: Found in approximately 50% of papillary thyroid carcinomas, 20% of anaplastic thyroid carcinomas, and in the more aggressive histological subtypes (e.g., tall cell).
BRCA1/2
What it is: BRCA1/2 genes encode proteins that help repair damage to both DNA chains through genetic recombination. If BRCA1/2 are non-functional then DNA damage accumulates.
BRCA1 and BRCA2 mutations can result from either gene (inherited) or somatic mutations.
Why the test is done::
1. Ovarian cancer. The presence of mutations that inactivate the BRCA1/2 genes predict sensitivity to PARP inhibitors.
2. Breast cancer. Women with BRCA mutation-associated breast cancer have up to a 40% chance of developing a new primary breast cancer within 10 years of diagnosis if untreated.
Frequency:
1. Approximately 25% of high-grade malignant serous carcinomas of the ovary
2. The frequency of BRCA1/2 mutations in breast cancer are found in 5-7% in the community.
EGFR
What it is: What it is: The EGFR (epidermal growth factor receptor) gene encodes a receptor for tyrosine kinase on the cell surface. Binding to the receptor leads to activation of the RAS, RAF and MEK signaling pathways, leading to uncontrolled cell proliferation. The most frequent mutations involve L858R and deletions of exon 19. Mutations in exon 20 cause resistance to treatment with tyrosine kinase inhibitors. In particular, the T790M mutation in exon 20 leads to resistance to first- and second-generation tyrosine kinase inhibitors (TKIs) but responds to third generation TKIs (osimertinib).
Why the test is done:: In NSCLC, the presence of EGFR mutations predict sensitivity to tyrosine kinase inhibitors.
Frequency: Approximately in 10-15% of the Western world
1. Mostly in non-smoking women
2. Most common in East Asia
3. More common in adenocarcinomas, and particularly in well-differentiated
HER-2
What it is: HER-2 encodes a receptor for tyrosine kinase that is located on the surface of cells. Binding to the receptor activates the RAS, RAF and MEK signaling pathways resulting in cell growth and proliferation. At the same time, enhancement of the HER-2 gene leads to overexpression of the protein making the cell prone to HER-2 activity and leading to uncontrolled cell proliferation.
Why the test is done: In carcinomas of the breast, stomach, colon, salivary glands and endometrial serous carcinomas, the presence of HER-2 biomarker amplification predicts the sensitivity of the neoplasm's response to treatment with anti-HER-2 monoclonal antibodies (e.g., trastuzumab, pertuzumab).
Frequency:
1. In 20% of breast carcinomas; Most common in high grade (Grade) malignancy (Grade) breast adenocarcinomas, without special features (NST)
2. Most often occurs in older individuals and in intestinal-type adenocarcinomas of the gastroesophageal junction
3. In 5% of colorectal carcinomas
4. In 50% of porogenic adenocarcinoma of the salivary glands and carcinoma of the plesiomorphic adenoma
5. In 25-30% of endometrial serous carcinoma
KIT
What it is: KIT encodes a tyrosine kinase receptor located on the cell surface. Binding to the receptor activates the RAS, RAF and MEK signaling pathways resulting in cell growth and proliferation.
Why the test is done:
1. GIST: The presence of KIT mutations predicts the sensitivity of the neoplasm to tyrosine kinase inhibitors (e.g., imatinib, sunitinib)
2. Melanoma: The presence of KIT mutations predicts the sensitivity of the neoplasm to tyrosine kinase inhibitors (e.g., imatinib)
Frequency:
1. Found in the majority of GISTs; approximately 60% of gastric GISTs and 90% of extra-gastrointestinal GISTs
2. In 1/3 of melanomas of the extremities
PDGFRA
What it is: PDGFRA encodes a tyrosine kinase receptor located on the cell surface. Binding to the receptor activates the RAS, RAF and MEK signaling pathways resulting in cell growth and proliferation.
Why the test is done:
GIST: The presence of PDGFRA mutations predicts neoplasm sensitivity to tyrosine kinase inhibitors (e.g., imatinib, sunitinib), while the D842V mutation is associated with treatment resistance.
Frequency: It is observed in approximately 10% of GISTs, predominantly of the stomach.
KRAS
What it is: The K-Ras protein encoded by the KRAS gene is part of the RAS/MAPK signaling pathway, whose activation leads to cell growth and cell proliferation. The most frequent mutations are found in codons 12 and 13.
Why the test is done:
1. Colorectal cancer: The presence of pathogenic KRAS (or NRAS) mutations predicts resistance to treatment with anti-EGFR monoclonal antibodies.
2. NSCLC: The presence of KRAS G12C mutations predicts sensitivity to KRAS inhibitors.
3. Thyroid cancer: The presence of KRAS (or NRAS/HRAS) mutations predicts a milder disease course.
Frequency: Found in 40-50% of colorectal cancers and 30% of NSCLC, with 10-15% having a KRAS-G12C mutation.
MMR
What it is: It is the DNA repair and maintenance mechanism (MMR) system responsible for repairing DNA damage consisting of the proteins MLH1, PMS2, MSH2 and MSH6. As a rule, MLH1 is inactivated either by mutations (usually gametic) or by hypermethylation of the gene initiator (usually somatic). In contrast, MSH2, PMS2 and MSH6 are most commonly inactivated by gametic mutations.
Gametic-type errors in MMR are observed in the following syndromes:
1. Lynch syndrome (autosomal dominant inheritance), characterized by an increased risk of colorectal, endometrial, urothelial, and upper gastrointestinal tract and pancreaticobiliary carcinomas.
2. Muir-Torre syndrome (autosomal dominant inheritance), which in addition to the above is characterised by neoplasms of the sebaceous glands and multiple keratoacanthomas.
3. Fundamental MMR deficiency syndrome (autosomal recessive inheritance), which is a rare entity characterized by the occurrence of cancers of the same type as Lynch syndrome, in addition to hematological tumours and neoplasms of the central nervous system. It is most commonly found in childhood and prepuberty.
A neoplasm that shows loss of expression of any MMR protein is considered to have a deficiency of the mismatched base repair mechanism (MMR deficient-dMMR).
Why the test is done:
1. In colorectal cancer, NICE (National Institute for Health and Clinical Excellence) guidelines recommend immunohistochemical testing for MMR deficiency in all first diagnosed tumours.
-Loss of expression may indicate gametic-type MMR deficiency, depending on the pattern of loss.
- The presence of MMR deficiency predicts susceptibility to immunotherapy with cancer checkpoint inhibitors.
- The presence of MMR deficiency also predicts a milder course of the disease.
2. In endometrial cancer, NICE guidelines recommend immunohistochemical testing for MMR deficiency in all newly diagnosed cancers.
-Loss of expression may indicate gametic-type MMR deficiency, depending on the pattern of loss.
- The presence of MMR deficiency predicts susceptibility to immunotherapy with cancer checkpoint inhibitors.
Frequency:
1. Approximately 15% of colorectal cancers, the majority of which are due to somatic mutations. Most commonly seen in right colon carcinomas of low differentiation and mucinous histological diversity accompanied by a strong immune response.
2. They are observed in 20-25% of endometrial carcinomas, the majority of which are due to somatic-type mutations. It is most frequently found in endometrioid and mixed carcinomas, as well as in undifferentiated and dedifferentiated endometrial neoplasms. In addition, they are mainly observed in carcinomas of high malignancy accompanied by a strong immune response.
MSI
What it is: Microsatellites are short, repeated DNA sequences. Microsatellite instability arises in MMR-deficient neoplasms and can arise either through somatic or gametic alterations.
Why the test is done: The test is performed for the same conditions for which MMR deficiency testing is performed. In general, immunohistochemical testing for MMR or microsatellite instability (MSI) testing provides similar rates of sensitivity and specificity and therefore both can be used.
NRAS
What it is: The NRAS gene encodes the N-Ras protein which is primarily involved in the control of cell division. Mutations in the NRAS gene activate the RAS-RAF-MAPK cellular pathway resulting in cell growth and cell proliferation. The most frequent mutations occur in codons 12 and 13.
Why the test is done:
1. Colorectal cancer. The presence of pathogenic NRAS (or KRAS) mutations predicts resistance to treatment with anti-EGFR monoclonal antibodies.
2. Melanoma. The presence of pathogenic NRAS mutations predicts, in part, sensitivity to MEK inhibitors (e.g., trametinib).
Frequency:
1. Found in 40-50% of colorectal carcinomas
2. Found in 15-20% of melanomas arising on both exposed and unexposed skin surfaces.
PD-L1
What it is: Neoplastic cells harbour a plethora of mutations and therefore produce a large number of defective proteins (neoantigens). Neoantigens are normally recognized as foreign by tumor cells resulting in their immune-induced destruction. Some tumours express immune checkpoints which bind to molecules on immune cells and cause them to either deactivate or undergo an apoptosis process. Checkpoint inhibitors prevent the function of checkpoints and thereby do not interfere with the immune-induced destruction of neoplastic cells.
Why the test is done:
1. NSCLC: PD-L1 expression levels determine patients' ability to receive either checkpoint inhibitor monotherapy (CSE) or in combination with chemotherapy (pembrolizumab).
2. Urothelial carcinoma: PD-L1 expression levels determine the compatibility of patients with ASE (atezolizumab, pembrolizumab).
3. Squamous cell carcinoma of the head/neck: PD-L1 expression levels determine the compatibility of patients with ASE (atezolizumab, nivolumab).
4. Esophageal cancer: PD-L1 expression levels determine the compatibility of patients with ASE (atezolizumab, nivolumab).
5. Triple negative breast cancer: PD-L1 expression levels determine the compatibility of patients with ASE (atezolizumab).
6. Melanoma: PD-L1 expression levels determine patients' eligibility to receive either ACE monotherapy or a combination of two ACEs (nivolumab or nivoluma-ipilimumab).
RET
What it is: The proto-oncogene RET encodes a receptor for tyrosine kinase that is located on the surface of cells. Binding to the receptor activates the RAS, RAF and MEK signaling pathways resulting in cell growth and proliferation.
Why the test is done:
1. 1. NSCLC: The presence of RET gene fusions predicts sensitivity to RET inhibitors (e.g., selpercatinib, pralsetinib)
2. Thyroid cancer: Presence of RET gene fusions predict sensitivity to RET inhibitors (selpercatinib)
Frequency:
1. 1. Found in approximately 1-2% of NSCLC and mainly in adenocarcinomas in non-smokers
2. Found in 10-20% of papillary thyroid carcinoma
ROS1
What it is: The proto-oncogene ROS1 encodes a tyrosine kinase receptor located on the cell surface. Binding to the receptor activates the RAS, RAF and MEK signaling pathways resulting in cell growth and proliferation.
Why the test is done: In NSCLC the presence of ROS1 rearrangements predict sensitivity to tyrosine kinase inhibitors (e.g., crizotinib)
Frequency: Found in approximately 1% of NSCLC, most commonly in adenocarcinomas and in non-smoking women
PIK3CA
What it is: The PIK3CA gene encodes the catalytic α-subunit of the PI3K signalling pathway which is involved in multiple biological functions of the cell and whose mutation results in uncontrolled cell proliferation. The most frequent mutations are found in exon 9 and 20.
Why the test is done:
1. Luminal A breast carcinomas: The presence of PIK3CA mutations predict sensitivity to PIK3CA inhibitors (e.g., alpelisib)
2. MMKP: The presence of PIK3CA mutations predict sensitivity to PIK3CA inhibitors
Frequency:
1. Found in 30-40% of hormone-sensitive breast carcinomas
2. Found in less than 5% of NSCLC and more frequently in squamous cell lung carcinomas
NTRK
What it is: The NTRK1, NTRK2 and NTRK3 genes encode on the cell surface the tyrosine kinase receptors TrkA, TrkB and TrkC. Binding to the receptor activates the RAS, RAF and MEK signaling pathways resulting in cell growth and proliferation. Transpositions lead to NTRK gene fusion resulting in uncontrolled cell proliferation.
Why the test is done:
NSCLC: The presence of NTRK gene fusions predict tumor response to tyrosine kinase inhibitors
Frequency: Found in 1.7% of NSCLC
MET
What it is: The proto-oncogene MET encodes a tyrosine kinase receptor that is located on the surface of cells. Binding to the receptor activates the RAS, RAF and MEK signaling pathways resulting in cell growth and proliferation.
Why the test is done: The international literature reports that enhancements in MET in NSCLC predict tumour response to tyrosine kinase inhibitors but have not yet been added to NICE guidelines. Furthermore, enhancement in MET constitutes a mechanism of secondary resistance to tyrosine kinase inhibitors in EGFR mutant NSCLC.
Frequency: Localized in 5% of NSCLCs.
MEN1
What it is: The MEN1 gene encodes the protein menin, which in turn acts as a tumour suppressor and has been associated with multiple endocrine neoplasia syndrome type 1. Menin controls epigenetic changes and affects chromatin structure through modification of histones.
Why the test is done:: it is tested in primary parathyroid hyperplasia for the coexistence of MEN1 syndrome.
Frequency: It is found in 1 in 30,000 people.
MDM2
What it is: The proto-oncogene MDM2 encodes the protein Mdm2 which acts to inhibit the tumor suppressor gene p53
Why the test is done: MDM2 gene amplification is localized, among others, in atypical lipomatous tumor/well-differentiated liposarcoma as well as in dedifferentiated liposarcoma, allowing their differential diagnosis from their mimics.
HPV detection and standardization
It concerns the molecular detection of human papillomavirus (HPV) by PCR and further typing of HPV strains. In this way, the possibility of HPV infection as well as infection with low or high-risk strains of the virus is checked.
Colorectal cancer predisposition panel
Panel of 17 genes associated with hereditary colorectal cancer. The screening is performed by next generation sequencing (NGS) and includes APC, MLH1, MSH2, MSH6, BMPR1A, CDH1, CHECK2, EPCAM, SMAD4, STK11, TP53, GREM1, MUTYH, PMS2, POLD1, POLE, PTEN.
Lynch syndrome panel
Panel of 5 genes associated with hereditary non-multipotent colorectal cancer (Lynch syndrome). The screening is done by next generation sequencing (NGS) and involves the genes EPCAM, MLH1, MSH2, MSH6 and PSM2..
Multipathology syndrome predisposition panel
Panel of 8 genes associated with familial adenomatous polyposis syndrome (FAP). The screening is done by next generation sequencing (NGS) and involves the genes BMPR1A, APC, MUTYH, NTHL1, POLE, POLD1, STK11, SMAD4..
Gastric cancer predisposition panel
Panel of 14 genes associated with gastric cancer. The screening is done by next generation sequencing (NGS) and includes CDH1, SDHB, SDHC, SDHD, SMAD4, STK11, APC, BMPR1A, EPCAM, MLH1, MSH2, MSH6, PMS2, TP53.
Pancreatic cancer predisposition panel
Panel of 17 genes associated with pancreatic cancer. The screening is done by next generation sequencing (NGS) and includes APC, PALB2, SMAD4, ATM, BMPR1A, BRCA1, BRCA2, CDK4, STK11, TP53, PMS2, CDKN2A, EPCAM, MEN1, MLH1, MSH2, MSH6.
Breast/ovarian cancer predisposition panel
Panel testing of 26 genes associated with hereditary pancreatic cancer. The screening is done by next generation sequencing (NGS) and includes BRCA1, BRCA2, BRIP1, PALB2, PMS2, POLD1, POLE, PTEN, RAD50, RAD51C, RAD51D, SMARCA4, STK11, TP53, CDH1, CHEK2, DICER1, ATM, BARD1, EPCAM, MLH1, MRE11, MSH2, MSH6, MUTYH, NBN.
Malignant melanoma predisposition panel
Panel Screening panel of 7 genes associated with malignant melanoma. The screening is done by next generation sequencing (NGS) and includes the genes BAP1, CDKN2A, PTEN, RB1, BRCA2, CDK4, TP53.
