Cancer nowadays is considered a pathology with a genetic component that occurs when cellular growth is out of control. Our body cells receive signals telling them when to grow and multiply and when such growth must stop. In a tumour, such cells do not respond to control signals and grow and multiply abnormally, spreading to different parts of the body, due to changes in their DNA.
The event leading to the alteration of genetic functions is called “mutation”. When a gene is affected by mutation for different causes (biological, chemical and physical), information to the cell will not be adequate for its functions.
Neoplasms are mostly pathologies caused by multiple factors generated by
genetic and environmental risk factors. Most tumours are “sporadic”, that is,
they arise in the general population without any clear signs of a genetic
susceptibility. In these types of tumours, DNA alterations (mutations) randomly
develop in somatic cells, namely, those cells creating every organ and system of
our body. These mutations develop in the DNA of a small group of cells and
generate the genetic error that is perpetrated in the descendants of those
cells. After having accumulated in an organ, they initially replace the healthy
cells of that organ and then spread to other organs, both nearby and distant
(metastasis). There are forms of tumour called "familial", when people
affected by cancer in the family are close relatives. Cancer familiarity is a
significant risk factor, especially when common environmental risk factors are
also shared (lifestyles, diet, polluting agents, etc.) without a specific
genetic alteration that makes the subject more susceptible to the disease.
Only a small, but significant, percentage of tumours are “hereditary”. Estimates
say that around 5-10% of breast cancers and 10-25% of ovarian cancers have a
hereditary component. In these tumours, DNA mutations occur in germ or
reproductive cell and, therefore, may be passed on to the person's offspring. At
birth, the child will show the genetic defect in one or more genes in all cells
of the body and, therefore, will be susceptible to the development of a neoplasm
when, during his/her life, other mutations occur. When a new person is
conceived, s/he acquires two pairs of each gene, one pair from the father and
one from the mother. Any genetic mutations in the DNA of the parents are,
therefore, passed on to children. If one of the parents has a mutation in one of
the cancer-generating genes (hereditary tumour), the offspring has a 50% chance
of inheriting that mutation. People inheriting a germ cell mutation are born
with a copy of the mutated gene. These people do not inherit the tumour, but
only the susceptibility to develop that type of cancer more easily, compared to
the general population.
is a diagnostic test developed by GENOMA Group, which carries out a multiple genetic analysis
aimed at evaluating the susceptibility to the development of breast and ovarian cancer. Therefore, the test identifies patients with the chance of developing the aforesaid neoplasms by analysing their DNA.
The genetic susceptibility test is addressed
to those people who, from a thorough
analysis of the family history, show a high
and concrete incidence of neoplasms in
previous generations and, therefore, have a
high chance of carrying a germinal mutation.
A hereditary form of cancer may be
present when the family has: • Several individuals affected by the
same type of cancer or correlated cancers,
• Individuals affected by multiple
tumours, • Tumours that arise at a young
The most significant signs are: • Breast
cancer diagnosed ≤ 45 years (especially when
diagnosed ≤ 35 years);•
Primary breast tumours in the same patient;
• Bilateral breast cancer; • Breast
cancer in males (at any age); • Ovarian
cancer in the family; • Breast and
ovarian cancer diagnosed in the same
patient; • Three or more cases of breast
cancer, ovarian cancer and/or pancreatic
cancer in the family; • Several members
of the family (on the same side) with breast
cancer or other types of cancer. •
Cancer in several members of the family in
different generations. • A known
mutation in the family in one of the genes
associated with breast/ovarian cancer
susceptibility. The geneticist, with
the informed consensus of the person, will
decide whether a DNA mutation diagnostic
test is necessary.
test is carried out with a blood sample. The DNA is
isolated from the nucleated cells through a
complex laboratory analysis and amplified via PCR.
Then, with a state-of-the art technological massive
parallel sequencing (MPS) process that uses
Next Generation Sequencing (NGS) techniques
with ILLUMINA sequencers, 13 genes
adjacent intrionic regions, ± 5 nucleotides) are
completely sequenced at high reading depth (Table
1). The chosen genes are often involved in
hereditary susceptibility to the formation of breast
and ovarian cancer; The resulting genetic
sequences are analysed with an advanced
bioinformatics analysis, to find mutations of the
examined genes, if present.
Present DNA sequencing techniques produce results with more than 99% accuracy. Even though this test is very accurate, the limits of the examination need to be considered.
This examination analyses only genetic diseases and genes listed in Table 1 and cannot detect:
• Mutations positioned in the intrionic regions beyond ± 5 nucleotides from the breakpoints;
• Deletions, inversions, or duplications with a value of more than 20 bps;
• Germline mosaicism (i.e. mutations only in the gametes).
A “NEGATIVE” - No mutations result for the examined genes does not exclude the possibility that mutations are not present in a region of the genome that was not explored during the examination.
Some regions of our DNA may not be sequenced or have a lower coverage than the limitations set by GENOMA Group experts to guarantee an accurate examination of gene variations. These regions, therefore, are not included in the examination if they do not meet the requested qualitative standards.
In some cases the result of genome testing may reveal DNA variations or mutations with an unknown or unclassifiable clinical meaning within the current medical and scientific knowledge.
The interpretation of genetic variations is based upon the most updated knowledge available upon examination. Such interpretation may change in the future, when new scientific and medical information on the structure of the genome are acquired and may affect the evaluation of the genetic variations themselves.
The possibility to detect subjects at risk of
developing a neoplasm is the best way for an early
diagnosis of cancer and, therefore, to decrease
mortality in that type of disease. Members of
families with high risks of inheriting cancer and
especially those that were directly affected by a
neoplasm may require genetic counselling and may
discuss his/her clinical and genetic situation with
the geneticist. This assessment may lead to a
genetic test to evaluate whether the patient is a
carrier of a mutation that increases susceptibility
to the development of a specific tumour. If the
test result is positive, the analysis may be
extended to the relatives of the patient, in order
to find those at risk.The information from
the genetic test may offer several benefits, such
Presence of one or more mutations:
result shows that there are one or more mutations in
one (or more) genes leading to hereditary
susceptibility to the development of breast and
ovarian cancer; the test, therefore, shows a mutated
copy of the gene. During a genetic consultancy
session, our geneticist thoroughly explains the test
results and calculates the likelihood of developing
the specific cancer associated to that mutation
detected in a specific gene.
A positive result does not necessarily mean that the patient with a mutation will develop a tumour; it only shows susceptibility to developing that type of tumour in the patient, or rather, the person has a higher risk level compared to a person without that specific mutation. In fact, not all people carrying mutations develop neoplasms. Although such mutations significantly increase the chance of developing a tumour, the cancer does not develop until the normal copy of the corresponding gene is mutated during the life of the person.
Since everyone inherits two pairs of the same gene, a mutation must occur in each pair to cancel the function of such gene. The acquisition of a new mutation may, therefore, directly lead to a tumour. Identifying cancer-susceptibility mutation allows us to develop an intense clinical check plan and evaluate preventive surgery. A mutation also leads to the examination of other relatives at risk if they want to check their situation. In relatives the test is a predictive analysis, because it detects, within these families, the carriers of the mutation and people that do not carry the mutation, finding exactly those people with a high chance of developing a tumour and those whose risk is at the same level as the general population. That way, carriers can start specific check protocols for early diagnosis or prevention, while the latter will be screened with the same protocols as the general population.
No mutations: the results show no mutations in the examined genes. However, a negative result does not necessarily mean that the patient does not risk developing a tumour. These people have the same chance of developing cancer as the general population because most of these types of tumours are sporadic in nature.
GENOMA is a highly specialised
diagnostic centre in Italy, renowned for its
contribution to the advancement of molecular
diagnostics. The laboratory is also renowned
internationally thanks to its collaboration with
scientific networks and prestigious research projects.
GENOMA, incorporated in 1997, is the point of
reference for high-tech examinations. It is mainly a
"service" centre for highly specialised prenatal and
postnatal genetic, cytogenetic and molecular
examinations.GENOMA is considered as one of the most
advanced molecular diagnostics centre in Europe and its
head offices are in Rome and Milan. The laboratories are
in a modern, high-tech building and cover a surface of
more than 4,000 sqm. The centre uses state-of-the-art
instruments and technologies and works at high quality
levels. GENOMA professionals have been working in
genetics for more than 20 years. A team of more than 100
professionals, including geneticists, molecular
biologists, gynaecologists, researches and laboratory
technicians work together operating in the field of
cytogenetic and molecular diagnostics for clinical
applications and research and are led by Dr. Francesco
Fiorentino inside a centre with very high technical and
scientific standards. GENOMA works all over Italy
and abroad in Europe, the United States and the Middle
East, providing specialised diagnostic support for
public and private health clinics, examination
laboratories, health centres, hospitals, private
clinics, general outpatients' clinics, medically
assisted procreation centres and physicians specialising
in different fields. Our laboratories receive
biological samples from more than 5,000 health centres
and hospitals every day. The integrated approach of the
Centre is aimed at performing extremely high volumes of
examinations; more than 100,000 genetic tests,
constantly increasing, are carried out every year.
One of the features of the Group is a well-organised
network of services, one of the most comprehensive in
Italy and abroad, allowing the centre to offer its
patients and their physicians innovative diagnostic
solutions for any clinical need. With a list of more
than 1,500 genetic tests available directly in our
laboratories and divided into 20 areas of application,
GENOMA is able to meet increasingly specialised requests
in cytogenetic and molecular diagnostics, providing its
customers with a highly specialised, precise, effective
and rapid service. GENOMA is a laboratory with one
of the longest, wide-ranging experience in Europe in
prenatal diagnostics. Thanks to this heritage, the Group
can offer expectant mothers and their physicians
state-of-the art technologies for foetal chromosome and
genetic diseases diagnostics.
2 main offices (Rome and Milan)
5,000 sqm dedicated to laboratories
100,000 genetic tests every year
1,500 types of genetic examinations
20 areas of application
If you want additional information on the BreastScreen®
test fill out the on-line form prepared by the
GENOMA laboratory and please do talk to one of the
staff in charge.
Via Castel Giubileo, 11 - 00138 Roma (RM)
Tel. : + (39) 06.8811270 (6 linee)
Fax : +(39) 06 64492025
Via Enrico Cialdini, 16 (Affori Centre)
20161 Milano (MI)
Tel. : + (39) 0239297626 (12 linee PBX)
Fax : + (39) 02392976261