Carter Jamal H, Cottrell Catherine E, McNulty Samantha N, Vigh-Conrad Katinka A, Lamp Stephen, Heusel Jonathan W, Duncavage Eric J
Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
Department of Pathology and Immunology, Washington University in St. Louis, Missouri 63130, USA.
Cold Spring Harb Mol Case Stud. 2017 Nov 21;3(6). doi: 10.1101/mcs.a001495. Print 2017 Nov.
is recurrently amplified in 5% of gastric cancers and 1%-4% of breast cancers; however, this molecular alteration has never been reported in a primary colorectal cancer specimen. Preclinical studies indicate that several FGFR tyrosine-kinase inhibitors (TKIs), such as AZD4547, have in vitro activity against the -amplified colorectal cell line, NCI-H716. The efficacy of these inhibitors is currently under investigation in clinical trials for breast and gastric cancer. Thus, better characterizing colorectal tumors for amplification could identify a subset of patients who may benefit from FGFR TKI therapies. Here, we describe a novel amplification identified by clinical next-generation sequencing in a primary colorectal cancer. Further characterization of the tumor by immunohistochemistry showed neuroendocrine differentiation, similar to the reported properties of the NCI-H716 cell line. These findings demonstrate that the spectrum of potentially clinically actionable mutations detected by targeted clinical sequencing panels is not limited to only single-nucleotide polymorphisms and insertions/deletions but also to copy-number alterations.
在5%的胃癌和1%-4%的乳腺癌中反复扩增；然而，这种分子改变从未在原发性结直肠癌标本中被报道过。临床前研究表明，几种FGFR酪氨酸激酶抑制剂（TKIs），如AZD4547，对扩增的结直肠癌细胞系NCI-H716具有体外活性。目前，这些抑制剂的疗效正在乳腺癌和胃癌的临床试验中进行研究。因此，更好地表征结直肠肿瘤的扩增情况可以识别出可能从FGFR TKI治疗中获益的患者亚组。在这里，我们描述了通过临床二代测序在原发性结直肠癌中鉴定出的一种新型扩增。通过免疫组织化学对肿瘤进行的进一步表征显示出神经内分泌分化，类似于已报道的NCI-H716细胞系的特性。这些发现表明，通过靶向临床测序 panel检测到的潜在可临床操作的突变谱不仅限于单核苷酸多态性和插入/缺失，还包括拷贝数改变。
