Solid malignancies in telomere biology disorders

Area of Science:

• Genetics and Molecular Biology
• Oncology
• Hematology

Background:

• Telomere biology disorders (TBDs) stem from genetic variants affecting telomere maintenance.
• These disorders lead to short/dysfunctional telomeres, causing bone marrow failure, organ damage, and immunodeficiencies.
• TBDs are cancer predisposition syndromes with a 3-fold increased cancer risk.

Purpose of the Study:

• To review recent advances in understanding solid malignancies in TBDs.
• To highlight the urgent need for prospective studies on cancer surveillance and treatment in TBDs.

Main Methods:

• Literature review of TBDs and associated solid malignancies.
• Analysis of cancer incidence, mechanisms, and treatment outcomes in TBD patients.

Main Results:

• Head/neck squamous cell carcinoma (HNSCC) risk is significantly elevated in TBDs (43-fold in AD, 276-fold in AR/XLR).
• Standard cancer treatments show poor tolerance and outcomes in TBDs.
• Mechanisms include chromosomal instability, DNA damage, immune deficiency, and clonal hematopoiesis.

Conclusions:

• There is an urgent need for prospective studies to establish evidence-based cancer surveillance and treatment protocols for TBDs.
• Understanding TBDs is crucial for managing associated cancer risks and improving patient outcomes.