分子景观和与非抑制性小肠粘性癌的克罗恩病的关联
Molecular Landscape and Association With Crohn Disease of Poorly Cohesive Carcinomas of the Nonampullary Small Bowel
影响因子:1.90000
分区:医学4区 / 病理学3区
发表日期:2023 Apr 04
作者:
Gianluca Tedaldi, Camilla Guerini, Davide Angeli, Daniela Furlan, Laura Libera, Marco Vincenzo Lenti, Federica Grillo, Matteo Fassan, Enrico Solcia, Fausto Sessa, Marco Paulli, Antonio Di Sabatino, Paola Ulivi, Alessandro Vanoli
摘要
凝聚性癌（PCC）的肿瘤是由单细胞或绳索样基质浸润的主要具有内粘性生长模式所定义的。与传统型小肠道腺癌相比，小肠PCC（SB-PCC）的临床性临床病理和预后特征直到最近才表征。但是，由于SB-PCC的遗传特征仍然未知，我们旨在分析SB-PCC的分子景观。通过Trusight Oncology 500在一系列15个非抑制性SB-PCC上进行下一代测序分析，进行了最常见的基因变化。基因的变化是TP53（53％）和Rhoa（53％）和Rhoa（13％）（13％）（13％）（13％）（13％）（13％）（13％）（13％），该基因，繁殖率（13％）（13％），繁殖，繁殖，繁殖，繁殖，繁殖率（13％），繁殖，繁殖，该基因的变化是繁殖的，该基因的变化是繁殖的，该基因的变化是繁殖的。未发现BRAF和PIK3CA突变。大多数SB-PCC（80％）与克罗恩病有关，其中包括rhoa-Mutated SB-PCC，具有非SRC型组织学，并且显示出奇特的阑尾型，低级别的杯状细胞细胞腺癌（GCA）类似类别。 SB-PCC很少会显示出较高的微卫星不稳定性，IDH1和ERBB2基因中的突变或FGFR2扩增（每种情况），在这种侵略性的癌症中建立或有希望的治疗靶标。 PIK3CA突变通常与结直肠癌和小肠腺癌相关，并不是这种癌症的典型特征。
Abstract
Poorly cohesive carcinomas (PCCs) are neoplasms defined by a predominantly dyshesive growth pattern with single cell or cord-like stromal infiltration. The -distinctive clinicopathologic and prognostic features of small bowel PCCs (SB-PCCs) in comparison with conventional-type small intestinal adenocarcinomas have only recently been characterized. However, as SB-PCCs' genetic profile is still unknown, we aimed to analyze the molecular landscape of SB-PCCs.A next-generation sequencing analysis through Trusight Oncology 500 on a series of 15 nonampullary SB-PCCs was performed.The most frequently found gene alterations were TP53 (53%) and RHOA (13%) mutations and KRAS amplification (13%), whereas KRAS, BRAF, and PIK3CA mutations were not identified. Most SB-PCCs (80%) were associated with Crohn disease, including both RHOA-mutated SB-PCCs, which featured a non-SRC-type histology, and showed a peculiar appendiceal-type, low-grade goblet cell adenocarcinoma (GCA)-like component. Rarely, SB-PCCs showed high microsatellite instability, mutations in IDH1 and ERBB2 genes, or FGFR2 amplification (one case each), which are established or promising therapeutic targets in such aggressive cancers.SB-PCCs may harbor RHOA mutations, which are reminiscent of the diffuse subtype of gastric cancers or appendiceal GCAs, while KRAS and PIK3CA mutations, commonly involved in colorectal and small bowel adenocarcinomas, are not typical of such cancers.