Radyasyonla İlişkili Kanserlerin Histopatolojik Özelikleri ve Moleküler İmzaları
Özet
Radyoterapi ve çevresel faktörler kaynaklı radyasyon maruziyeti, uzun vadede sekonder malignitelerin gelişimine yol açabilmektedir. İyonizan radyasyon, hücresel düzeyde DNA çift sarmal kırıklarına ve kronik oksidatif strese neden olarak malign transformasyonları tetikler. Nadir durumlar haricinde, radyasyon ilişkili kanserleri sporadik eş değerlerinden ayırt edecek özgül histopatolojik bulgular oldukça kısıtlıdır. Bu nedenle tanısal süreçlerde, tümörlerin moleküler imzalarından yararlanılmaktadır. Örneğin, radyasyon ilişkili papiller tiroid kanserlerinde RET/PTC3 gen füzyonları ve CLIP2 aşırı ekspresyonu dikkat çekerken; sekonder meme anjiyosarkomlarında MYC ve FLT4 amplifikasyonları ayırt edici rol oynar. Benzer şekilde, radyasyon ilişkili gliomlar PDGFRA amplifikasyonu ve CDKN2A/B kaybı ile karakterize bir moleküler profil sergiler. Akciğer dokusunda ise radon maruziyeti, yüksek tümör mutasyon yükü ve DNA onarım mekanizmalarında bozulmalarla ilişkilendirilmiştir. Gelecekte, transkriptom analizleri ve DNA metilasyon profilleme gibi ileri tekniklerin entegrasyonu, radyasyona sekonder gelişen bu tümörlerin patogenezinin aydınlatılmasında ve hedef tedavilerin optimize edilmesinde kritik bir önem taşımaktadır.
Radiation therapy and environmental radiation exposure can lead to the long-term development of secondary malignancies. At the cellular level, ionizing radiation induces DNA double-strand breaks and chronic oxidative stress, triggering malignant transformations. Exceptional cases aside, specific histopathological findings distinguishing radiation-induced cancers from sporadic counterparts remain extremely limited. Consequently, diagnostic processes heavily leverage unique molecular signatures. For instance, radiation-associated papillary thyroid carcinomas frequently exhibit RET/PTC3 gene fusions and CLIP2 overexpression, whereas secondary breast angiosarcomas are characterized by MYC and FLT4 amplifications. Similarly, radiation-induced gliomas display a distinct molecular profile defined by PDGFRA amplification and CDKN2A/B loss. In lung tissue, radon exposure correlates with a high tumor mutational burden and defects in DNA repair pathways. Looking ahead, integrating advanced techniques like transcriptome analysis and DNA methylation profiling is of paramount importance to elucidate the molecular pathogenesis of these secondary tumors and optimize targeted therapeutic strategies.
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