Levine Cancer Institute, Atrium Health, Charlotte, NC.
Tempus Labs Inc, Chicago, IL.
JCO Precis Oncol. 2022 Mar;6:e2100245. doi: 10.1200/PO.21.00245.
Promising single-agent activity from sotorasib and adagrasib in -mutant tumors has provided clinical evidence of effective KRAS signaling inhibition. However, comprehensive analysis of -variant prevalence, genomic alterations, and the relationship between and immuno-oncology biomarkers is lacking.
Retrospective analysis of deidentified records from 79,004 patients with various cancers who underwent next-generation sequencing was performed. Fisher's exact test evaluated the association between cancer subtypes and variants. Logistic regression assessed comutations with other oncogenes and the association between variants and immuno-oncology biomarkers.
Of the 79,004 samples assessed, 13,758 (17.4%) harbored mutations, with 1,632 (11.9%) harboring and 12,126 (88.1%) harboring other variants (). Compared with across all tumor subtypes, was more prevalent in females (56% 51%, false discovery rate-adjusted value [FDR-] = .0006), current or prior smokers (85% 56%, FDR- < .0001), and patients age > 60 years (73% 63%, FDR- ≤ .0001). The most frequent variants across all subtypes were G12D (29.5%), G12V (23.0%), G12C (11.9%), G13D (6.5%), and G12R (6.2%). was most prevalent in patients with non-small-cell lung cancer (9%), appendiceal (3.9%), colorectal (3.2%), tumor of unknown origin (1.6%), small bowel (1.43%), and pancreatic (1.3%) cancers. Compared with -mutated, -mutated tumors were significantly associated with tumor mutational burden-high status (17.9% 8.4%, odds ratio [OR] = 2.38; FDR- < .0001). -mutated tumors exhibited a distinct comutation profile from -mutated tumors, including higher comutations of (20.59% 5.95%, OR = 4.10; FDR- < .01) and (15.38% 4.61%, OR = 3.76; FDR- < .01).
This study presents the first large-scale, pan-cancer genomic characterization of . The mutation was more prevalent in females and older patients and appeared to be associated with smoking status. tumors exhibited a distinct comutation profile and were associated with tumor mutational burden-high status.
在 - 突变肿瘤中，索托拉西布和阿达格拉西布的单一药物活性令人鼓舞，为 KRAS 信号抑制的有效性提供了临床证据。然而，缺乏对 - 变体流行率、基因组改变以及 和免疫肿瘤标志物之间关系的综合分析。
对 79004 名接受下一代测序的各种癌症患者的匿名记录进行回顾性分析。Fisher 精确检验评估了癌症亚型与 变异之间的关联。逻辑回归评估了 与其他致癌基因的共突变以及 变异与免疫肿瘤标志物之间的关系。
在评估的 79004 个样本中，13758 个（17.4%）携带 突变，其中 1632 个（11.9%）携带 ，12126 个（88.1%）携带其他 变体（）。与所有肿瘤亚型相比， 在女性中更为普遍（56%比 51%，经错误发现率调整的 值[FDR-] =.0006），当前或以前的吸烟者（85%比 56%，FDR- <.0001）和年龄> 60 岁的患者（73%比 63%，FDR- ≤.0001）。所有亚型中最常见的 变体是 G12D（29.5%）、G12V（23.0%）、G12C（11.9%）、G13D（6.5%）和 G12R（6.2%）。 在非小细胞肺癌（9%）、阑尾（3.9%）、结直肠癌（3.2%）、来源不明肿瘤（1.6%）、小肠（1.43%）和胰腺癌（1.3%）患者中最为普遍。与 突变相比， 突变的肿瘤与肿瘤突变负担高状态显著相关（17.9%比 8.4%，比值比[OR] = 2.38；FDR- <.0001）。 突变的肿瘤与 突变的肿瘤具有明显不同的共突变谱，包括更高的 共突变（20.59%比 5.95%，OR = 4.10；FDR- <.01）和 共突变（15.38%比 4.61%，OR = 3.76；FDR- <.01）。
本研究首次对 进行了大规模的泛癌种基因组特征描述。 突变在女性和老年患者中更为常见，似乎与吸烟状态有关。 肿瘤表现出独特的共突变谱，并与肿瘤突变负担高状态相关。
