therapeutics. Then, we also have the issue of balancing the sensitivity and the specificity of
these technologies if we plan to routinely use them to screen an asymptomatic population
for early signs of cancer and perform tumor monitoring, which are the goals of the liquid
biopsy revolution. Continuous efforts in protocol improvement and algorithm development
should bring us closer to making this a reality.
Of course, the implementation of a “genomic medicine for all” approach also carries
ethical issues that need to be carefully considered. For example, every whole-genome
sequencing of a cancer patient may also identify secondary findings unrelated to the disease
of interest, for example, a genetic variant that increases risk to Alzheimer’s disease in a
breast cancer patient. Discussions are still on-going as to whether to report these findings to
the patients. Another potential area of consideration is privacy and security of the patient’s
genetic information and its implications to the patient’s relatives, as well as the definition of
“informed consent” [55].
Finally, we must not forget that even though genomics is set to revolutionize our
knowledge of cancer biology and the clinical care of cancer patients, it can still tell us
only part of the story. Other fields, such as immunohistochemistry, histopathology, radiation oncology, imaging procedures in radiology, and molecular biology are equally necessary if we want to have a holistic view of the chain of events necessary for cancer
development as well as to provide the best care to patients. There is no doubt that an
interdisciplinary approach will help researchers and clinicians deliver on the promise of
precision medicine.
Take Home Message
• Genes are drivers if their somatic mutation aids cancer growth. These can be
classified into oncogenes (genes whose activation leads to tumor development),
tumor suppressors (genes whose inactivation supports neoplastic transformation),
and gene fusions (a product of two genes that gains a novel ability). These genes
carry different mutation patterns.
• Sequencing has aided cancer diagnosis by facilitating gene panel testing and
whole-exome/genome sequencing.
• Mutational signatures are patterns of mutations that can be extracted via computational analysis of large cohorts of tumors, and which can be informative about
the processes that gave rise to a tumor.
• Bulk genome sequencing of large numbers of tumors has allowed the identification of mutational drivers, the classification of tumors in genomic subtypes, and
revealed dysregulated processes critical for tumor growth.
• Single-cell DNA and RNA sequencing of cancers can reveal their biological
complexity at an unprecedented level, examples include the amount of intratumor heterogeneity and drug resistance mechanisms.
(continued)
2 Opportunities and Perspectives of NGS Applications in Cancer Research
33
these technologies if we plan to routinely use them to screen an asymptomatic population
for early signs of cancer and perform tumor monitoring, which are the goals of the liquid
biopsy revolution. Continuous efforts in protocol improvement and algorithm development
should bring us closer to making this a reality.
Of course, the implementation of a “genomic medicine for all” approach also carries
ethical issues that need to be carefully considered. For example, every whole-genome
sequencing of a cancer patient may also identify secondary findings unrelated to the disease
of interest, for example, a genetic variant that increases risk to Alzheimer’s disease in a
breast cancer patient. Discussions are still on-going as to whether to report these findings to
the patients. Another potential area of consideration is privacy and security of the patient’s
genetic information and its implications to the patient’s relatives, as well as the definition of
“informed consent” [55].
Finally, we must not forget that even though genomics is set to revolutionize our
knowledge of cancer biology and the clinical care of cancer patients, it can still tell us
only part of the story. Other fields, such as immunohistochemistry, histopathology, radiation oncology, imaging procedures in radiology, and molecular biology are equally necessary if we want to have a holistic view of the chain of events necessary for cancer
development as well as to provide the best care to patients. There is no doubt that an
interdisciplinary approach will help researchers and clinicians deliver on the promise of
precision medicine.
Take Home Message
• Genes are drivers if their somatic mutation aids cancer growth. These can be
classified into oncogenes (genes whose activation leads to tumor development),
tumor suppressors (genes whose inactivation supports neoplastic transformation),
and gene fusions (a product of two genes that gains a novel ability). These genes
carry different mutation patterns.
• Sequencing has aided cancer diagnosis by facilitating gene panel testing and
whole-exome/genome sequencing.
• Mutational signatures are patterns of mutations that can be extracted via computational analysis of large cohorts of tumors, and which can be informative about
the processes that gave rise to a tumor.
• Bulk genome sequencing of large numbers of tumors has allowed the identification of mutational drivers, the classification of tumors in genomic subtypes, and
revealed dysregulated processes critical for tumor growth.
• Single-cell DNA and RNA sequencing of cancers can reveal their biological
complexity at an unprecedented level, examples include the amount of intratumor heterogeneity and drug resistance mechanisms.
(continued)
2 Opportunities and Perspectives of NGS Applications in Cancer Research
33