1196例黑色素瘤的年龄相关下一代测序突变分析

Age-related next-generation sequencing mutational analysis in 1196 melanomas.

作者信息

Santamaria-Barria Juan A, Matsuba Chikako, Khader Adam, Scholar Anthony J, Garland-Kledzik Mary, Fischer Trevan D, Essner Richard, Salomon Matthew P, Mammen Joshua M V, Goldfarb Melanie

机构信息

Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Computational Biology Division, Saint John's Cancer Institute at Providence St. John's Health Center, Santa Monica, California, USA.

出版信息

J Surg Oncol. 2023 Jun;127(7):1187-1195. doi: 10.1002/jso.27239. Epub 2023 Mar 20.

DOI:10.1002/jso.27239

PMID:36938777

Abstract

BACKGROUND AND OBJECTIVES

Melanoma mutational burden is high and approximately 50% have oncogenic mutations in BRAF. We sought to evaluate age-related mutational differences in melanoma.

METHODS

We analyzed melanoma samples in the Genomics Evidence Neoplasia Information Exchange database. Targetable mutations were identified using the Precision Oncology Knowledge Base (OncoKB).

RESULTS

We found 1194 patients with a common set of 30 genes. The top mutated genes in patients <40 years old (y/o) (n = 98) were BRAF (59%), TP53 (31%), NRAS (17%), and PTEN (14%); in 40-59 y/o (n = 354) were BRAF (51%), NRAS (30%), TP53 (26%), and APC (13%); and in ≥60 y/o (n = 742) were BRAF (38%), NRAS (33%), TP53 (26%), and KDR (19%). BRAF mutations were almost mutually exclusive from NRAS mutations in <40 y/o (58/59). Mutational burden increased with age, with means of 2.39, 2.92, and 3.67 mutations per sample in patients <40, 40-59, and ≥60 y/o, respectively (p < 0.0001). There were 10 targetable mutations meeting OncoKB criteria for melanoma: BRAF (level 1), RET (level 1), KIT (level 2), NRAS (level 3A), TP53 (level 3A), and FGFR2, MET, PTEN, PIK3CA, and KRAS (level 4).

CONCLUSIONS

Mutations in melanoma have age-related differences and demonstrates potential targetable mutations for personalized therapies.

摘要

背景与目的

黑色素瘤的突变负荷较高，约50%的患者存在BRAF致癌突变。我们试图评估黑色素瘤中与年龄相关的突变差异。

方法

我们分析了基因组证据肿瘤信息交换数据库中的黑色素瘤样本。使用精准肿瘤知识库（OncoKB）识别可靶向突变。

结果

我们发现了1194例具有一组30个常见基因的患者。年龄小于40岁（y/o）（n = 98）的患者中，突变频率最高的基因是BRAF（59%）、TP53（31%）、NRAS（17%）和PTEN（14%）；40 - 59岁（n = 354）的患者中是BRAF（51%）、NRAS（30%）、TP53（26%）和APC（13%）；60岁及以上（n = 742）的患者中是BRAF（38%）、NRAS（33%）、TP53（26%）和KDR（19%）。在年龄小于40岁的患者中，BRAF突变与NRAS突变几乎相互排斥（58/59）。突变负荷随年龄增加，年龄小于40岁、40 - 59岁和60岁及以上的患者每个样本的平均突变数分别为2.39、2.92和3.67（p < 0.0001）。有10种可靶向突变符合黑色素瘤的OncoKB标准：BRAF（1级）、RET（1级）、KIT（2级）、NRAS（3A级）、TP53（3A级）以及FGFR2、MET、PTEN、PIK3CA和KRAS（4级）。