Fleming Andrew M, Gehle Daniel B, Freitas Julia Pedo, Hendrick Leah E, Yakoub Danny, Abdelhafeez Hafeez, Nezakatgoo Nosratollah, Deneve Jeremiah L, Langham Max R, Glazer Evan S, Shibata David, Merchant Nipun B, Dickson Paxton V, Murphy Andrew J
Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
J Surg Oncol. 2024 Oct;130(5):1051-1061. doi: 10.1002/jso.27808. Epub 2024 Aug 19.
Solid pseudopapillary neoplasm (SPN) of the pancreas demonstrates an indolent disease course; however, some patients present with a "malignant" phenotype, including distant metastases resistant to chemotherapy. This analysis identifies molecular drivers of metastatic SPN using the world's largest clinicogenomics database.
The American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange was queried for primary and metastatic SPN samples. Sample-level genomic alterations were compared. A pan-pancreatic cancer analysis assessed relevant mutations among all metastatic pancreatic malignancies.
Among 28 SPN samples identified (n = 17 primary, n = 11 metastatic), the most commonly mutated gene was CTNNB1, (24/28 samples; 85.7%). Most mutations were missense (21/24; 87.5%) or in-frame deletions (3/24; 12.5%). The most common CTNNB1 mutations in primary SPN were exon 3 S37F/C missense mutations (6/16 profiled patients, 37.5%), contrasting exon 3 D32N/Y/H missense mutations in metastatic samples (6/11 profiled patients, 54.5%). Metastatic SPN had higher rates of CTNNB1 mutations than metastases from pancreatic ductal adenocarcinoma (72.7% vs. 1.1%; q < 0.0001), pancreatic neuroendocrine tumor (72.7% vs. 2.5%; q < 0.0001), and pancreatic acinar cell carcinoma (72.7% vs. 11.5%; q = 0.0254).
Missense mutations along exon 3 of CTNNB1 predominate metastatic SPN, differentiating these patients from those with metastases from analogous pancreatic malignancies.
胰腺实性假乳头状瘤（SPN）病程进展缓慢；然而，部分患者呈现出“恶性”表型，包括对化疗耐药的远处转移。本分析利用全球最大的临床基因组学数据库确定转移性SPN的分子驱动因素。
在美国癌症研究协会的肿瘤基因组学证据肿瘤信息交换项目中查询原发性和转移性SPN样本。比较样本水平的基因组改变。一项全胰腺癌分析评估了所有转移性胰腺恶性肿瘤中的相关突变。
在鉴定出的28例SPN样本中（n = 17例原发性，n = 11例转移性），最常发生突变的基因是CTNNB1（24/28例样本；85.7%）。大多数突变是错义突变（21/24；87.5%）或框内缺失（3/24；12.5%）。原发性SPN中最常见的CTNNB1突变是外显子3的S37F/C错义突变（16例分析患者中的6例，37.5%），而转移性样本中则是外显子3的D32N/Y/H错义突变（11例分析患者中的6例，54.5%）。转移性SPN的CTNNB1突变率高于胰腺导管腺癌转移灶（72.7%对1.1%；q < 0.0001）、胰腺神经内分泌肿瘤转移灶（72.7%对2.5%；q < 0.0001）和胰腺腺泡细胞癌转移灶（72.7%对11.5%；q = 0.0254）。
CTNNB1外显子3的错义突变在转移性SPN中占主导，将这些患者与类似胰腺恶性肿瘤转移患者区分开来。
