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甲状腺乳头状癌和结直肠癌中的复发性体细胞突变

Recurrent Somatic Mutations in Papillary Thyroid Cancer and Colorectal Cancer.

作者信息

Bu Rong, Siraj Abdul K, Masoodi Tariq, Parvathareddy Sandeep Kumar, Iqbal Kaleem, Al-Rasheed Maha, Haqawi Wael, Diaz Mark, Victoria Ingrid G, Aldughaither Saud M, Al-Sobhi Saif S, Al-Dayel Fouad, Al-Kuraya Khawla S

机构信息

Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Department of Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

出版信息

Front Oncol. 2021 May 11;11:670423. doi: 10.3389/fonc.2021.670423. eCollection 2021.

Abstract

is a dual specificity protein kinase that phosphorylates both threonine and tyrosine residues in . mutations have been identified in several cancers. However, their role in Middle Eastern papillary thyroid cancer (PTC) and colorectal cancer (CRC) is lacking. In this study, we evaluated the prevalence of mutations in a large cohort of Middle Eastern PTC and CRC using whole-exome and Sanger sequencing technology. In the discovery cohort of 100 PTC and 100 CRC cases (comprising 50 mutant and 50 wildtype cases each), we found one mutation each in PTC and CRC, both of which were wildtype. We further analyzed 286 PTC and 289 CRC wildtype cases and found three mutant PTC cases and two mutant CRC cases. Thus, the overall prevalence of mutation in wildtype cases was 1.1% (4/336) in PTC and 0.9% (3/339) in CRC. Histopathologically, three of the four mutant PTC cases were follicular variant and all four tumors were unifocal with absence of extra-thyroidal extension. All the three CRC cases harboring mutation were of older age (> 50 years) and had moderately differentiated stage II/III tumors located in the left colon. In conclusion, this is the first comprehensive report of somatic mutations prevalence in PTC and CRC from this ethnicity. The mutually exclusive nature of and mutations suggests that each of these mutation may function as an initiating mutation driving tumorigenesis through signaling pathway.

摘要

是一种双特异性蛋白激酶,可磷酸化其中的苏氨酸和酪氨酸残基。在几种癌症中已鉴定出 突变。然而,它们在中东乳头状甲状腺癌(PTC)和结直肠癌(CRC)中的作用尚不清楚。在本研究中,我们使用全外显子组测序和桑格测序技术评估了一大群中东PTC和CRC中 突变的发生率。在100例PTC和100例CRC病例的发现队列中(每组包括50例 突变型和50例野生型病例),我们在PTC和CRC中各发现1例 突变,两者均为 野生型。我们进一步分析了286例PTC和289例CRC 野生型病例,发现3例 突变型PTC病例和2例 突变型CRC病例。因此, 野生型病例中 突变的总体发生率在PTC中为1.1%(4/336),在CRC中为0.9%(3/339)。组织病理学上,4例 突变型PTC病例中有3例为滤泡变体,所有4个肿瘤均为单灶性,无甲状腺外侵犯。所有3例携带 突变的CRC病例年龄较大(>50岁),肿瘤为中度分化的II/III期,位于左结肠。总之,这是该种族PTC和CRC中 体细胞突变发生率的首份综合报告。 突变和 突变的互斥性质表明,这些突变中的每一个都可能作为起始突变,通过 信号通路驱动肿瘤发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d090/8144646/b3f0cda1b060/fonc-11-670423-g001.jpg

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