Studying the melanomas most often overlooked

For decades, melanoma research has largely focused on ultraviolet-driven tumours arising in sun-exposed skin, which predominate in light-skinned populations. As a result, acral melanoma—a subtype considered rare overall but amongst the most common forms of melanoma in patients with skin of color—has remained critically understudied. Acral melanoma has also gained public attention through high-profile cases, including that of musician Bob Marley, who died from the disease in 1981. Despite this visibility, the molecular drivers underlying its often aggressive clinical behaviour remain incompletely understood.

At the Rosalind and Morris Goodman Cancer Institute (GCI), the laboratory of Dr. Simon Roy, M.D., M.H.S., is working to change this narrative by rethinking how rare melanomas are studied, diagnosed, and treated.

Bridging clinical insight and molecular discovery

An Assistant Professor in the Department of Pathology, Dr. Roy is a clinician-scientist and dermatopathologist who divides his time between the McGill University Health Centre and the Rosalind and Morris Goodman Cancer Institute. While diagnosing skin cancers in the clinic, he also leads a research program focused on uncovering their molecular underpinnings. This dual perspective directly informs the laboratory’s core questions, particularly around acral melanomas, which are often diagnosed at later stages and respond less predictably to standard therapies.

“As a dermatopathologist, I see how these tumours often present later and behave more aggressively,” says Dr. Roy. “For many patients, particularly those with darker skin, the disease does not always fit the patterns on which many diagnostic frameworks and risk models are based. That disconnect is what drives our research questions.”

These clinical realities inform the laboratory’s scientific focus on understanding why acral melanoma behaves differently and how its distinct biology might be targeted more effectively.

Redesigning research pipelines for inclusion

One feature of the Roy laboratory’s work is its deliberate effort to address gaps created by historically non-representative research cohorts. Many existing biomarkers and predictive models in melanoma have been developed using datasets that may not fully reflect the diversity of patients affected by the disease. This limitation can compromise diagnostic accuracy and treatment decision-making.

To address this challenge, the Roy lab uses and develops integrated bioinformatic pipelines that combine genome-wide DNA methylation profiling, spatial gene expression mapping, and protein localization studies. These approaches enable the identification of regulatory pathways active within specific regions of the tumour microenvironment and allow molecular signatures to be linked to clinical outcomes.

These analyses are paired with ancestry-specific genotyping, using SNP-based approaches to characterize the genetic ancestries of study participants. This strategy supports the development of predictive models that account for genetic diversity rather than relying on one-size-fits-all assumptions.

Studying acral melanoma where it matters most

The laboratory’s work is particularly focused on acral melanoma—a subtype that arises on the palms, soles, and nail beds and is not linked to ultraviolet exposure. While rare in the general population, acral melanoma represents the most common melanoma subtype in patients with skin of color and is associated with poorer survival outcomes.

“Acral melanoma is often labeled as rare, but that classification depends on who you study,” says Dr. Roy. “For patients with skin of color, it is one of the most common melanoma subtypes, yet we still know far less about its biology than we should.”

Using a combination of circulating tumour DNA analysis and tissue-based studies, the team is mapping epigenetic patterns associated with disease progression. Genome-wide methylation profiling is used to identify key regulatory regions, while spatial transcriptomics allows researchers to examine how epigenetically regulated pathways function within distinct tumour niches. By correlating these molecular features with clinical data, the laboratory is generating multidimensional maps of melanoma biology. This work is being recently funded through the Marathon of Hope Cancer Centres Network Clinician Scientist fund, awarded to Dr. Roy for his work on acral melanoma epigenetics.

From discovery to patient-relevant impact

To bridge laboratory discoveries with clinical application, the Roy lab employs precision-cut tumour slice cultures that preserve the native three-dimensional architecture of patient tumours. This ex vivo platform maintains the complex cellular interactions of the tumour microenvironment, enabling the testing of drug combinations and the modelling of therapeutic responses in a context that closely reflects human disease.

Together, these approaches support the laboratory’s overarching objective: to develop non-invasive biomarkers for early detection and treatment monitoring, while addressing a critical research gap affecting historically underrepresented patient populations.

Strengthening cancer research through equity

By focusing on what melanoma research has historically overlooked, the Roy laboratory is demonstrating how inclusive research design strengthens scientific discovery. Studying diverse patient populations is not simply a matter of representation, it is essential for building accurate models of disease and improving outcomes across populations.