Bult Johanna A A, Plaça Jessica R, Haacke Erlin A, Terpstra M Martijn, Verstappen Gwenny M, Spijkervet Frederik K L, Kroese Frans G M, Plattel Wouter J, Vermaat Joost S P, Bootsma Hendrika, van der Vegt Bert, Diepstra Arjan, van den Berg Anke, Kok Klaas, Nijland Marcel
Department of Hematology, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
Department of Pathology and Medical Biology, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
Cancers (Basel). 2022 Feb 17;14(4):1010. doi: 10.3390/cancers14041010.
Patients with primary Sjogren's syndrome (pSS) are at risk of developing extranodal marginal zone lymphoma (ENMZL) of the mucosa-associated lymphoid tissue (MALT) in the parotid glands. Unlike recurrent genomic aberrations observed in MALT lymphoma, which were not associated with pSS (non-pSS), it is unknown which somatic aberrations underlie the development of pSS-associated MALT lymphomas. Whole-exome sequencing was performed on 17 pSS-associated MALT lymphomas. In total, 222 nonsynonymous somatic variants affecting 182 genes were identified across the 17 cases. The median number of variants was seven (range 2-78), including three cases with a relatively high mutational load (≥24/case). Out of 16 recurrently mutated genes, , , , and are known to be associated with lymphomagenesis. A total of 18 copy number alterations were detected in eight cases. translocations were not detected. With respect to outcome, only two cases relapsed outside of the salivary glands. Both had a high mutational load, suggesting a more advanced stage of lymphoma. The low mutational load and lack of a clear lymphoma-related mutation profile suggests that localized pSS-associated MALT lymphomas are genomically more stable than non-pSS MALT lymphomas and most likely depend on a stimulatory micro-environment.
原发性干燥综合征（pSS）患者有发生腮腺黏膜相关淋巴组织（MALT）结外边缘区淋巴瘤（ENMZL）的风险。与在MALT淋巴瘤中观察到的复发性基因组畸变不同，后者与pSS（非pSS）无关，目前尚不清楚哪些体细胞畸变是pSS相关MALT淋巴瘤发生的基础。对17例pSS相关MALT淋巴瘤进行了全外显子测序。在这17例病例中，共鉴定出222个影响182个基因的非同义体细胞变异。变异的中位数为7个（范围2 - 78），包括3例具有相对较高突变负荷（≥24/例）的病例。在16个反复突变的基因中，已知 、 、 、 和 与淋巴瘤发生有关。在8例病例中检测到总共18个拷贝数改变。未检测到 易位。关于预后，只有2例在唾液腺外复发。两者都有较高的突变负荷，提示淋巴瘤处于更晚期阶段。低突变负荷和缺乏明确的淋巴瘤相关突变谱表明，局限性pSS相关MALT淋巴瘤在基因组上比非pSS MALT淋巴瘤更稳定，并且很可能依赖于刺激性微环境。
