Applicability of Routine Targeted Next-generation Sequencing to Estimate Tumor Mutational Burden (TMB) in Patients Treated With Immune Checkpoint Inhibitor Therapy

被引：2

作者：

Pinato, David J. ^{[1
,2
]}

Urus, Heather ^{[1
,2
]}

Newsom-Davis, Thomas ^{[3
]}

Du Parcq, Persephone ^{[4
]}

Belessiotis, Katherine ^{[2
]}

Mapara, Leah ^{[2
]}

Gupta, Nandita ^{[5
]}

Power, Danielle ^{[2
]}

Weir, Justin ^{[5
]}

Wong, Ching Ngar ^{[1
]}

Ratnakumaran, Ragu P. ^{[2
]}

Dominy, Kathy ^{[4
]}

Khorashad, Jamshid ^{[4
]}

Bower, Mark ^{[3
]}

机构：

[1] Imperial Coll London, Dept Surg & Canc, London, England

[2] Imperial Coll NHS Trust, Charing Cross Hosp, Dept Oncol, London, England

[3] Chelsea & Westminster Hosp, Dept Oncol, London, England

[4] Hammersmith Hosp, Mol Pathol Lab, London, England

[5] Imperial Coll NHS Trust, Hammersmith Hosp, Dept Histopathol, London, England

来源：

JOURNAL OF IMMUNOTHERAPY | 2020年 / 43卷 / 02期

基金：

英国惠康基金;

关键词：

TMB; immunotherapy; targeted; NGS; panel;

D O I：

10.1097/CJI.0000000000000295

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

It remains unclear whether targeted next-generation sequencing (tNGS) conveys a reliable estimate of tumor mutational burden (TMB). We sequenced 79 archival samples of immune checkpoint inhibitors (ICPIs) recipients (57% lung cancer, 43% melanoma) using Ion Ampliseq Cancer Hotspot Panel. Employing multiple cutoff values, we verified that TMB by tNGS did not correlate with response or survival following ICPI. We found enrichment of ATM mutations in ICPI-refractory tumors (P=0.01) to correlate with worse survival (4.2 vs. 10 mo, P=0.03). Limited-coverage tNGS delivers an imprecise estimate of patients' TMB but may aid identification of candidate somatic variants of predictive/prognostic significance.

引用

页码：53 / 56

页数：4

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