So, how is rare cancer different from regular cancer? And why should there be separate awareness?
September 30th is annual Rare Cancer Day for awareness, spearheaded by the NORD Rare Cancer Coalition® under the National Organization for Rare Disorders (NORD) [1]. The day focuses on the unique challenges of rare cancers and the patients, families, and researchers who face them.
What is Rare Cancer?
- A rare cancer is typically defined as one that occurs in fewer than 15 per 100,000 people per year [2].
- Examples include sarcomas, some brain tumors, and certain gastrointestinal cancers.
- In contrast, common cancers—like breast, lung, colon, or prostate—affect thousands or millions each year.
- While individually uncommon, rare cancers as a group account for just over a quarter of all cancers and nearly a third of cancer deaths [3].
How Rare Cancers Differ From Common Cancers
| Aspect | Rare Cancer | Common Cancer |
| Incidence | Very low | High |
| Research & data | Limited clinical trials, sparse data | Large studies, many trials, well-established guidelines |
| Treatment options | Often experimental or borrowed from other cancers | Standardized, widely available therapies |
| Diagnosis | Often delayed or misdiagnosed due to unfamiliarity | Usually recognized early, standard tests exist |
| Prognosis | Often poorer due to delayed diagnosis & limited treatments | Prognosis well-understood, survival improving |
Why Separate Awareness Matters
Rare cancer patients face unique challenges: delayed diagnosis, limited treatment options, and a shortage of clinical trials and expert centers. Research progress is often hindered by the scarcity of patient samples and data.
- Visibility: Rare cancers can be “invisible” in public and medical discourse. Awareness days help shine a spotlight.
- Funding & research: Rare cancers often get less research funding; awareness drives investment.
- Patient support: Patients with rare cancers may feel isolated—awareness connects them to resources, communities, and clinical trials.
- Policy & advocacy: Highlighting the challenges unique to rare cancers helps influence healthcare policy and access to treatments.
So, even though all cancers are serious, the above barriers are precisely why awareness initiatives such as Rare Cancer Day are so vital. Every September is a focused day to educate, fundraise, and advocate.
Rare Cancer Origin
A crucial question to think about in cancer care is this: was it inherited?
Imagine a patient, let’s call her Sarah, diagnosed at age 32 with a rare, aggressive soft-tissue sarcoma—a tumor type that strikes fewer than 15 in every 100,000 people annually [2]. Sarah’s physicians correctly identified the malignant cells, but a nagging question remained, one that has profound implications for her treatment and her family’s future: Where did the cancer truly begin?
Is the pathogenic variant responsible for Sarah’s tumor somatic, meaning it was sporadically acquired randomly over her lifetime, confined to the tumor cells? Or is it germline, an inherited predisposition passed down through generations, present in virtually every cell of her body?
The Germline vs. Somatic Dilemma: An Analogy
Consider this analogy. Imagine a house representing the patient’s body:
- A somatic mutation is like a fire that started in the kitchen. It is confined, sporadic, and must be extinguished.
- A germline variant is like a flaw in the original blueprint, present in every room. While the fire may appear in one place first, the structural flaw means the entire house—and even other houses built from the same design (the family)—is at risk.
This analogy underscores why interpretation matters.
Take the example of a germline TP53 variant, which causes Li-Fraumeni Syndrome (LFS) [4]. If a variant is misclassified as somatic, treatment focuses only on the tumor. If correctly identified as germline, the clinical approach expands:
- Modified Treatment: Avoiding therapies like radiation, which can trigger secondary cancers in LFS patients.
- Intensive Surveillance: Rigorous screening, including whole-body MRI, to detect new tumors early.
- Family Cascade Genetic Testing: Counseling and genetic testing for relatives, enabling preventive care.
For many rare cancers, especially those diagnosed at a young age or appearing in multiple family members, the underlying driver is an inherited germline genetic variant. Identifying it via genetic testings and counselling informs prognosis, guides precision treatment, and enables preventive care for the patient’s family.
With it comes massive volumes of Next-Generation Sequencing (NGS) data. Yet, processing and interpretation remain highly complex, requiring consideration of factors such as low variant allele frequency, normal tissue contamination, and benign variants that complicate classification.
Automated pipelines that enable standardized, in-depth exploration of relevant NGS data are transforming this process. A well-designed platform empowers researchers to perform deep, accurate genetic analysis, unlocking meaningful insights from NGS data at scale.
Why Does Rare Cancer Awareness Efforts Often Focus On Genetics / Germline Variants?
- Inherited risk is often more visible
- While common cancers are usually influenced by a mix of lifestyle and environment, many rare cancers have a stronger link to inherited genetic variants.
- Example: Certain soft-tissue sarcomas, medullary thyroid cancer, or rare pancreatic cancers often appear in families with known cancer syndromes.
- Early detection and precision care
- If a rare cancer is suspected to have a germline (inherited) component, testing can reveal whether other family members are at risk.
- This knowledge guides tailored screening, prevention, and treatment strategies, instead of a “one-size-fits-all” approach.
- Treatment options may be genetics-driven
- Rare cancers often lack standard therapies, so understanding the genetic cause can open doors to targeted therapies or clinical trials.
- For instance, tumors with certain DNA repair defects may respond well to specific drugs that wouldn’t be considered otherwise.
- Research acceleration
- Studying the genetic drivers of rare cancers helps scientists uncover new cancer pathways that can benefit both rare and common cancers.
- Rare cancers can act like a “genetic magnifying glass” for cancer biology.
Genetics isn’t just an academic detail; it is often the key to diagnosis, treatment, and family risk management in rare cancers. That’s why awareness campaigns frequently emphasize genetic testing and counseling alongside education and advocacy.
On this Rare Cancer Day, Compass Bioinformatics reaffirm our solidarity with the estimated 25 million Americans living with a rare disease [5], many of whom face rare cancers. High-precision variant interpretation is no longer optional; it is the foundation of effective Precision Oncology.
Compass Bioinformatics proudly supports the rare disease community and the clinician researchers who serve them, helping accelerate genetic analysis and deliver faster, data-driven answers.
| Learn more about how InheriNext AI variant interpretation addresses the data analysis bottleneck, equipping users with faster, more reliable results.
We encourage our colleagues in oncology and genetics to continue advancing awareness, research, and care. Explore resources at the NORD Rare Cancer Coalition: rarediseases.org [1]. The NORD Rare Cancer Coalition unites over 30 advocacy organizations to amplify rare cancer research, advocacy, and patient access [1].
To the clinicians, geneticists, and researchers: What is your biggest challenge in distinguishing germline from somatic variants in rare cancer work? Share your perspective with us so we can turn challenges into actionable bioinformatics solutions.
References
[1] National Organization for Rare Disorders (NORD). Rare Cancer Day.
[2] National Cancer Institute (NCI). Definition of rare cancer.
[3] NCI Pediatric and Adult Rare Tumor Program.
[4] Li-Fraumeni Syndrome Association. What Is LFS?
[5] National Organization for Rare Disorders (NORD). Rare Disease Facts.