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Massive parallel sequencing in a family with rectal cancer
Hereditary Cancer in Clinical Practice ( IF 1.7 ) Pub Date : 2021-04-07 , DOI: 10.1186/s13053-021-00181-2
Karin Wallander , Jessada Thutkawkorapin , Ellika Sahlin , Annika Lindblom , Kristina Lagerstedt-Robinson

We have previously reported a family with a suspected autosomal dominant rectal and gastric cancer syndrome without any obvious causative genetic variant. Here, we focused the study on a potentially isolated rectal cancer syndrome in this family. We included seven family members (six obligate carriers). Whole-exome sequencing and whole-genome sequencing data were analyzed and filtered for shared coding and splicing sequence and structural variants among the affected individuals. When considering family members with rectal cancer or advanced adenomas as affected, we found six new potentially cancer-associated variants in the genes CENPB, ZBTB20, CLINK, LRRC26, TRPM1, and NPEPL1. All variants were missense variants and none of the genes have previously been linked to inherited rectal cancer. No structural variant was found. By massive parallel sequencing in a family suspected of carrying a highly penetrant rectal cancer predisposing genetic variant, we found six genetic missense variants with a potential connection to the rectal cancer in this family. One of them could be a high-risk genetic variant, or one or more of them could be low risk variants. The p.(Glu438Lys) variant in the CENPB gene was found to be of particular interest. The CENPB protein binds DNA and helps form centromeres during mitosis. It is involved in the WNT signaling pathway, which is critical for colorectal cancer development and its role in inherited rectal cancer needs to be further examined.

中文翻译:

直肠癌家族中的大规模并行测序

我们以前曾报道过一个家庭,怀疑其常染色体显性遗传性直肠和胃癌综合症,而没有任何明显的致病基因变异。在这里,我们将研究重点放在这个家庭中潜在的孤立性直肠癌综合症上。我们包括了七个家庭成员(六个专职承运人)。分析了全外显子测序和全基因组测序数据,并筛选了受影响个体之间共享的编码和剪接序列以及结构变体。当考虑患有直肠癌或晚期腺瘤的家庭成员时,我们在CENPB,ZBTB20,CLINK,LRRC26,TRPM1和NPEPL1基因中发现了六个新的可能与癌症相关的变异。所有变体都是错义变体,以前没有基因与遗传性直肠癌相关。没有发现结构变异。通过在怀疑携带高渗透性直肠癌易感基因变异的家庭中进行大规模平行测序,我们发现了六个遗传错义变异体,与该家族的直肠癌有潜在联系。其中之一可能是高风险的遗传变异,或者其中一个或多个可能是低风险的变异。发现CENPB基因中的p。(Glu438Lys)变体特别令人关注。CENPB蛋白结合DNA并在有丝分裂过程中帮助形成着丝粒。它参与了WNT信号通路,这对于结直肠癌的发展至关重要,其在遗传性直肠癌中的作用需要进一步研究。其中之一可能是高风险的遗传变异,或者其中一个或多个可能是低风险的变异。发现CENPB基因中的p。(Glu438Lys)变体特别令人关注。CENPB蛋白结合DNA并在有丝分裂过程中帮助形成着丝粒。它参与了WNT信号通路,这对于结直肠癌的发展至关重要,其在遗传性直肠癌中的作用需要进一步研究。其中之一可能是高风险的遗传变异,或者其中一个或多个可能是低风险的变异。发现CENPB基因中的p。(Glu438Lys)变体特别令人关注。CENPB蛋白结合DNA并在有丝分裂过程中帮助形成着丝粒。它参与了WNT信号通路,这对于结直肠癌的发展至关重要,其在遗传性直肠癌中的作用需要进一步研究。
更新日期:2021-04-08
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