Developed to assess genomic instability through a simple blood test
HELIXPACE
Monitoring genomic instability—namely the accumulation of genetic mutations—is key to primary cancer prevention and to reducing the risk of future tumour development
HELIXPACE is a test designed to detect genetic instability (also referred to as genomic instability) through a peripheral blood sample.
This parameter is assessed by monitoring the frequency of mutations and represents a key indicator of the prodromal phase of solid tumours. The DNA extracted from the sample is sequenced using advanced Next Generation Sequencing (NGS) technologies. The subsequent bioinformatic analysis enables the identification of potential mutations in the genes under investigation.
HELIXPACE investigates and quantifies the presence of mutations in both tumour suppressor genes and driver genes, with the aim of assessing their effectiveness in preserving genomic stability. When repeated over time, the test can reveal a progressive accumulation of somatic mutations, which would support the persistent inactivation of these genes and the resulting genomic instability.
Origin of Somatic Mutations
From embryonic development onwards, an individual’s DNA undergoes thousands of daily damages due to a wide range of environmental, chemical, or biological factors such as:
- Genotoxicity
- Mutagenic chemical substances
- Tobacco smoke
- DNA replication errors
- Oxidative stress
- Ultraviolet radiation
- Ionising radiation
- Environmental pollution
- Viruses
These damages are normally repaired by Tumour Suppressor Genes, thereby preventing the development of serious diseases such as cancer. These genes play a fundamental role in the cellular response, promoting the repair of damaged DNA, preventing uncontrolled cell proliferation, and inhibiting cancerous transformation.
Impact on DNA and Ageing Processes
When Tumor Suppressor Genes lose their function, damage goes unrepaired and transforms into Somatic Mutations that can compromise genomic stability. Temporary loss of gene function is not critical, whereas permanent inactivation results in a progressive accumulation of somatic mutations, which characterizes the prodromal phase of carcinogenesis, known as Genomic Instability.
Genomic Instability is thus an indicator of Tumor Suppressor Gene inactivity. These genes play key roles in regulating the cell cycle, DNA repair, and programmed cell death of damaged cells. When inactive, the cell loses vital control mechanisms that normally protect against cancer development. This loss can lead to multiple consequences that facilitate neoplastic transformation and tumour progression.
In addition to Tumour Suppressor Genes, HELIXPACE also investigates whether somatic mutations are present in Driver Genes. When mutated or abnormally expressed, these genes push cells towards cancerous transformation and contribute directly to tumour growth and survival.
Genomic Instability is considered a primary cause of ageing and age-related diseases, such as cancer. The progressive accumulation of somatic mutations (Genomic Instability) identified by HELIXPACE suggests that critical genome control mechanisms, typically governed by Tumour Suppressor and Driver Genes, are not functioning correctly, leading to an acceleration of associated pathologies.
Health Consequences
The time required for cancer development, starting from the first signs of genomic instability, varies greatly and depends on numerous factors.
There is no fixed or predictable timeframe within which a cell with an inactive Tumour Suppressor Gene and Genomic Instability becomes cancerous.
Generally, the process can take from a few years to several decades. For instance, some forms of leukaemia may develop relatively quickly, while other cancers, such as prostate or breast cancer, may take many years to emerge from a single altered cell. Each case can differ significantly depending on specific circumstances.
Conventional Approaches to Restoring Tumour Suppressor Gene Function
Various approaches have been developed to attempt the restoration of Tumour Suppressor Gene function or to mitigate the effects of their inactivation. The main strategies for gene reactivation include the use of DNA-demethylating agents and gene therapy, which involves introducing a functional copy of the Tumour Suppressor Gene.
STRATEGIES FOR THE REACTIVATION OF TUMOUR SUPPRESSOR GENES
Identify Gene Inactivation
Recognise inactive Tumour Suppressor Genes
Apply Gene Therapy
Introduce a functional copy
Administer Drugs
Use pharmacological agents to restore protein function
Modify DNA
Chemically modify DNA to restore function
Restore Gene Function
Achieve reactivation of tumour suppressor gene function
HELIXPACE: Innovative Genomic Monitoring Backed by Scientific Evidence
The accumulation of genetic alterations and epigenetic changes over a person’s lifetime can lead to genomic instability in normal cells. The immune system recognises and eliminates most mutated cells, but some may evade this control and initiate tumour development.
Liquid biopsy, being minimally invasive, allows longitudinal monitoring over time in healthy individuals of tissue progression events from normal to precancerous and eventually neoplastic conditions.
The genes analysed with the HELIXPACE test were selected based on current scientific literature, data from clinical studies, and guidelines provided by the NCCN (National Comprehensive Cancer Network).
Comprehensive Analysis
The HELIXPACE test is performed by analysing circulating nucleic acids (DNA and RNA) extracted from the patient’s plasma (cell-free total nucleic acid, cfTNA).
Specifically, the panel includes 52 genes and evaluates over 900 SNVs (single nucleotide variations), 12 CNV-gains (copy number increases), and 99 gene fusions. Additionally, for the MET gene, the test assesses the exon 14 splicing (skipping) mutation.
- Hotspot Genes (SNVs) and small insertions/deletions (indels): APC, AKT1, ALK, AR, ARAF, BRAF, CHEK2, CTNNB1, DDR2, EGFR, ERBB2, ERBB3, FBXW7, ESR1, FGFR1, FGFR2, FGFR3, FGFR4, FLT3, GNA11, GNAQ, GNAS, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MAP2K2, MET, MTOR, NRAS, NTRK1, NTRK3, PDGFRA, PIK3CA, PTEN, RAF1, RET, ROS1, SF3B1, SMAD4, SMO, TP53
- Gene fusions: ALK, BRAF, ERG, ETV1, FGFR1, FGFR2, FGFR3, MET, NTRK1, NTRK3, RET, ROS1
- De novo (non-hotspot) variants in TP53: The panel covers approximately 80% of the TP53 gene. Detected non-HS variants are reported if their allelic frequency is ≥ 1%.
- MET exon 14 skipping
- Ma Copy number amplifications (CNAs): CCND1, CCND2, CCND3, CDK4, CDK6, EGFR, ERBB2, FGFR1, FGFR2, FGFR3, MET, MYC
Under optimal conditions, the test can detect sequence variants with an allelic frequency greater than 0.1%. The Limit Of Detection (LOD) achieved in the analysis for each patient is provided in the technical report.
EXTENDED DIAGNOSTIC PROTOCOL
As part of an integrated approach, it is recommended to complement the analysis of systemic inflammation with the following tests, which form the BIOXPACE protocol :
SENEXPACE
SENEXPACE – analyses cellular senescence, a natural defence mechanism that prevents the uncontrolled proliferation of cells with damaged DNA and, consequently, high tumourigenic potential. Senescent cells release inflammatory signals that generate and spread inflammation throughout the body, thereby triggering systemic inflammation.
CYTOXPACE
CYTOXPACE – assesses key markers of systemic inflammation that, when altered, are associated with accelerated aging processes, increased genotoxicity, and genomic instability, conditions that increase the risk of disease onset.
IMMUNEXPACE
IMMUNEXPACE – evaluates the balance and effectiveness of the immune system in carrying out its functions. The immune system helps counteract systemic inflammation by eliminating senescent cells that fuel inflammatory processes. When the immune system is weakened, these cells are not adequately removed and therefore accumulate in tissues, contributing to chronic inflammation.
GUTXPACE
GUTXPACE – analyses the gut microbiome to identify and characterize the microorganisms present in the intestinal tract. The balance of intestinal bacteria is one of the main modulators of immune responses. Gut health directly influences the effectiveness of the immune system, including its ability to clear senescent cells that drive systemic inflammation.(LINK)
NANOXPACE
NANOXPACE – detects and quantifies nano- and microplastics in the bloodstream. The immune system recognizes these foreign substances, triggering an inflammatory response. The progressive accumulation of nano/microplastics contributes to genotoxicity and therefore genomic instability, which in turn accelerates degenerative processes and ageing.
