与APC相关的多个唾液腺损伤:空间转录组分析显示WNT的渐进激活
Fiona Chan-Pak-Choon1,2, Catherine Beaumont3, José Camacho Valenzuela1,4
1Department of Human Genetics, McGill University, Montreal, QC, Canada.
The Journal of pathology
|August 29, 2025
概括
减弱的家族腺瘤多样性 (AFAP) 与新的唾液腺瘤有关. 这项研究确定了基底细胞腺瘤和腺癌是潜在的AFAP表型,扩大了对疾病的理解.
科学领域:
- 癌症学
- 遗传学
- 病理学
背景情况:
- 减弱家族腺瘤多样性 (AFAP) 是由于APC基因变异导致结直肠癌风险的遗传性疾病.
- 唾液腺瘤是罕见的,以前没有与AFAP有关.
研究的目的:
- 研究AFAP与唾液腺瘤之间的关联.
- 探索AFAP患者唾液腺瘤发展的分子机制.
主要方法:
- 一个家庭的病例研究 AFAP 和多个唾液腺瘤.
- 对瘤样本进行β-catenin染色,APC局部变异 (CNN-LOH) 和CTNNB1突变的分析.
- 唾液病变的空间转录组分析以评估WNT通路的基因表达.
主要成果:
- 这项研究确定了AFAP家族中的基底细胞腺瘤 (BCA) 和基底细胞腺癌 (BCAC).
- 在结肠和唾液腺瘤中观察到异常的核β-catenin染色.
- 基因组分析显示,巴状BCAC的APC位点发生变化,以及下状BCAC的CTNNB1突变.
- 从良性到恶性的唾液病变,WNT通路基因表达逐渐增加.
结论:
- 基底细胞腺瘤和腺癌是AFAP的潜在新表型.
- 在AFAP中,APC功能丧失和WNT通路激活与这些唾液腺瘤的发展有关.
- 这扩大了AFAP的临床范围,并突出了WNT途径在其发病过程中的作用.
相关概念视频
Canonical Wnt Signaling Pathway
8.9K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.9K
Non-Canonical Wnt Signaling Pathways
7.4K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.4K
Tumor Progression
6.5K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.5K
Pleiotropy
41.1K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
41.1K


