Comprehensive cytogenetic study of primary cutaneous gamma-delta T-cell lymphoma by means of spectral karyotyping and genome-wide single nucleotide polymorphism array

• Published in: Cancer genetics 2012-09, Vol.205 (9), p.459-464
• Main Authors: Yamamoto-Sugitani, Mio, Kuroda, Junya, Shimura, Yuji, Nagoshi, Hisao, Chinen, Yoshiaki, Ohshiro, Muneo, Mizutani, Shinsuke, Kiyota, Miki, Nakayama, Ryuko, Kobayashi, Tsutomu, Uchiyama, Hitoji, Matsumoto, Yosuke, Horiike, Shigeo, Taniwaki, Masafumi
• Format: Article
• Language: English
• Subjects: DNA Copy Number Variations; Female; Genome, Human; Genome-wide single nucleotide polymorphism analysis; Hematology, Oncology and Palliative Medicine; Humans; Lymphoma, T-Cell, Cutaneous - genetics; Medical Education; Middle Aged; Oligonucleotide Array Sequence Analysis - methods; Polymorphism, Single Nucleotide; primary cutaneous gamma-delta T-cell lymphoma; Receptors, Antigen, T-Cell, gamma-delta - genetics; spectral karyotyping; Spectral Karyotyping - methods
• ISSN: 2210-7762; 2210-7770
• DOI: 10.1016/j.cancergen.2012.05.006

Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL), which originates from activated mature gamma-delta T cells with a cytotoxic phenotype is a rare T-cell lymphoproliferative disease. The prognosis of PCGD-TCL has been rather unfavorable due to poor response to conventional chemotherapy, and its molecular features and pathophysiology underlying disease development remain unknown. We report here a case with primarily treatment-resistant PCGD-TCL featuring highly complex cytogenetic and genetic aberrations detected by spectral karyotyping and genome-wide single nucleotide polymorphism (SNP) array. Chromosomal aberrations included several chromosomal translocations involving breakpoints at 9p21, 14q11.2, 14q32.1, or 16q23.1, suggesting the involvement of WWOX , TCL gene cluster, and BCL11B , which are crucial for tumorigenesis in T-cell lymphomas. SNP analysis also identified genome copy number gains and losses in various regions, which can potently deregulate expression of various pro- and anti-oncogenic genes involved in RAS-related protein pathways, PI3K/AKT/MTOR-related pathways, MYC-related signaling, or TP53 - related signaling. Thus, this case report may shed some light on the complex molecular abnormalities involved in the development of PCGD-TCL and on information that can aid the search for druggable target molecules in this disease.