Genomics of acral lentiginous melanoma (IRAS 241746)

Melanoma is rare among skin cancers, but it causes most skin cancer deaths. In Mexico, the most common form is acral lentiginous melanoma, a type that often goes unnoticed until it's advanced, leaving just over half of patients alive five years after diagnosis. We're analysing tumour samples gathered over decades at the National Cancer Institute of Mexico, using genetic sequencing to uncover the mutations driving this disease and the factors that put people at risk. Understanding these genetic fingerprints could help doctors spot warning signs earlier, develop targeted treatments, and shape prevention campaigns suited to Mexican patients.

Melanoma accounts for only 4% of dermatological cancers but causes 75% of skin cancer deaths. In Mexico, the predominant histopathological subtype is acral lentiginous melanoma (ALM), which carries a poor prognosis, with only 52.3% of patients surviving beyond five years. Despite this burden, the mutational landscape of ALM and the genetic factors influencing its development and prognosis remain poorly understood.

This study will analyse tumour samples held by the National Cancer Institute of Mexico, collected as part of the ongoing ‘Mutational Profile of Lentiginous Acral Melanoma’ study, using sequencing and genotyping approaches. The work aims to characterise the mutational landscape of ALM, identify mutational signatures linked to key prognostic indicators such as ulceration, and detect genetic risk factors for disease development in Mexican patients. Findings will inform the development of targeted therapeutic strategies and support evidence-based prevention and public health initiatives.

Rationale

Completion of this study will bring us closer to understanding the mutational landscape of ALM and the genetic risk factors in Mexicans. This will, in turn, allow problems such as the development of therapeutic strategies targeting specific molecular lesions, as well as prevention strategies and public health campaigns to be addressed.

Aims

The study aims to:

• define the mutational landscape of ALM (acral lentiginous melanoma) to identify mutational signatures associated with important predictors of survival such as ulceration and to detect genetic factors that elevate the risk of developing ALM.

Primary Outcome

Somatic mutation frequencies in ALM samples and correlation of these with clinical characteristics such as ulceration, tumour thickness, tumour site, etc.

Key Secondary outcome(s)

None

Study Type

Observational

Participant and Sample Information

Populations involved:

Individuals with a histopathological diagnosis of acral lentiginous
melanoma in Mexico.

Countries of recruitment:

International

Approximate participant or sample numbers (if applicable):

up to 500

Key inclusion criteria:

1. Patients of the National Cancer Institute of Mexico with a histopathological diagnosis of acral lentiginous
   melanoma.
2. Patients with material available for analysis: Blocks of paraffin and/or frozen tissue with enough material for diagnosis and sequencing,
   and/or the presence of primary tumour, regional or metastasis at an appropriate distance from the primary lesion.
3. Patients with follow-up clinical data for at least 12 months.
4. Patients that have signed the informed consent sheet for the ‘Mutational profile of Lentiginous Acral Melanoma’
   study currently running at the National Cancer Institute, Mexico.

Key exclusion criteria:

1. Patients with a histologically unconfirmed diagnosis of acral lentiginous melanoma.
2. Patients with a melanoma diagnosis with no material available for analysis and with no biopsies taken
3. Patients for whom the national Cancer Institute, Mexico has no follow-up information.
4. Patients that have not signed the informed consent sheet for the ‘Mutational profile of Lentiginous Acral Melanoma’
   study currently running at the National Cancer Institute, Mexico.

Recruitment status:

Non-recruiting: Pre-collected samples only.

Governance and Ethical Approval

Governance and oversight:

Study Sponsor: Wellcome Sanger Institute

All work conducted at the Wellcome Sanger Institute is reviewed and overseen by institutional Research Governance processes, ensuring compliance with ethical, legal, and regulatory requirements.

Ethical approval:

This study has been reviewed by the East of England – Cambridgeshire and Hertfordshire NHS Research Ethics Committee. The study received REC approval on 1 March 2018.

IRAS 241746

REC reference: 18/EE/0076

Data and Sample Use

Data sharing:

Anonymised DNA sequence data are stored in the European Genome-Phenome Archive (EGA) and made available to bonafide researchers via managed access, subject to data access agreements. Anonymised samples and cultured cells may also be shared with other legitimate research organisations under appropriate legal agreements.

IPD sharing statement

Deidentified individual participant-level data (IPD) will not be shared as part of this study.

Completion date 

Ongoing

Further Information

For enquiries about the scientific aims of this study or potential collaboration, please contact the relevant scientific programme at [CI email address].

For enquiries relating to research governance, ethics, or regulatory oversight, please contact the Research Governance team at researchgovernance@sanger.ac.uk.