Abstract
TP53 is frequently mutated in different types of neoplasms including leukemia and lymphomas. Mutations of TP53 have also been reported in mycosis fungoides (MF), the most common type of cutaneous lymphoma. However, little is known about the frequency, spectrum of mutations, and their prognostic significance in MF. In this study, we have optimized the protocol for Sanger sequencing of TP53 using DNA extracted from archival paraffin-embedded biopsies. Of 19 samples from patients with stage IIB MF or higher, 31% harbored mutations in TP53. Overall survival of the patients with mutated TP53 was significantly shorter than median survival in the age- and stage-matched patients treated in our Institution. Distribution of mutations was heterogenous in TP53 exons; however, C > T transitions were common suggesting the causal role of ultraviolet radiation. We propose that TP53 mutation status would be useful for risk stratification of patients with advanced MF.
Highlights
Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL) and in most cases runs an indolent course
The tumor suppressor gene TP53 is central in tumorigenesis and regarded as a master regulator of several signaling pathways involved in this process
In this study we wished to elucidate the p53 in Cutaneous Lymphoma frequency and potential role of TP53 mutations in mycosis fungoides (MF) according to disease stage and course
Summary
Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL) and in most cases runs an indolent course. Approximately 20% of patients would progress to a widespread disease with multiple skin tumors and extracutaneous involvement with dire outcome [1]. While low-grade lymphoid neoplasms reveal low p53 mutation rates, lymphomas and leukemias (in particular chronic lymphatic leukemia) with an aggressive clinical course demonstrate higher frequencies [4,5,6,7]. To this end, a strong correlation was found between p53 functional status and clinical outcomes in lymphoma, such as mortality or resistance to chemotherapy [8, 9]. We have developed a method, which enables TP53 sequencing from paraffin-embedded samples from a relatively large number of patient samples
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