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. 2020 Dec;34(12):3413-3419.
doi: 10.1038/s41375-020-1000-0. Epub 2020 Aug 5.

Whole-genome sequencing identifies responders to Pembrolizumab in relapse/refractory natural-killer/T cell lymphoma

Jing Quan Lim #  1   2   3 , Dachuan Huang #  2   3 , Tiffany Tang #  4 , Daryl Tan #  5   6 , Yurike Laurensia  2 , Rou-Jun Peng  1 , Esther Kam Yin Wong  2 , Daryl Ming Zhe Cheah  2 , Burton Kuan Hui Chia  2 , Jabed Iqbal  7 , Nicholas Francis Grigoropoulos  6 , Maarja-Liisa Nairismägi  2 , Cedric Chuan Young Ng  8   9 , Vikneswari Rajasegaran  8   9 , Huangming Hong  1   10 , Seok Jin Kim  11 , Junhun Cho  12 , Eric Tse  13 , Benjamin Mow  14 , Qi-Chun Cai  15 , Li-Mei Poon  16 , Qing-Qing Cai  1 , Jing Tan  1   2   8 , Jason Yongsheng Chan  4 , Johnathan Xiande Lim  7 , Yeow Tee Goh  6 , Colin Phipps  6 , Olaf Rötzschke  17 , Chee Leong Cheng  7 , Jeslin Chian Hung Ha  18 , Lay Poh Khoo  18 , Yvonne Su Ming Loh  5   6 , Rex Au-Yeung  19 , Thomas Sau-Yan Chan  13 , Yok-Lam Kwong  13 , William Hwang  20 , Won Seog Kim  11 , Jin-Xin Bei  1 , Tongyu Lin  21   22 , Choon Kiat Ong  23   24   25 , Soon Thye Lim  26   27
Affiliations

Whole-genome sequencing identifies responders to Pembrolizumab in relapse/refractory natural-killer/T cell lymphoma

Jing Quan Lim et al. Leukemia. 2020 Dec.

Erratum in

  • Correction to: Whole-genome sequencing identifies responders to Pembrolizumab in relapse/refractory natural-killer/T cell lymphoma.
    Lim JQ, Huang D, Tang T, Tan D, Laurensia Y, Peng RJ, Wong EKY, Cheah DMZ, Chia BKH, Iqbal J, Grigoropoulos NF, Nairismägi ML, Ng CCY, Rajasegaran V, Hong H, Kim SJ, Cho J, Tse E, Mow B, Cai QC, Poon LM, Cai QQ, Tan J, Chan JY, Lim JX, Goh YT, Phipps C, Rötzschke O, Cheng CL, Ha JCH, Khoo LP, Loh YSM, Au-Yeung R, Chan TS, Kwong YL, Hwang W, Kim WS, Bei JX, Lin T, Ong CK, Lim ST. Lim JQ, et al. Leukemia. 2021 Apr;35(4):1225. doi: 10.1038/s41375-021-01195-4. Leukemia. 2021. PMID: 33686199 Free PMC article. No abstract available.
No abstract available

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Conflict of interest statement

JQL, CKO and STL are co-inventors of the patent filed under International Application No. PCT/SG2018/050509 by Singapore Health Services Pte Ltd which is related to this work. At the time of writing, the co-inventors did not receive honoraria for this work. The patent has been licensed to Lucence (did not take part in this study).

Figures

Fig. 1
Fig. 1. PD-L1 structural rearrangements (PD-L1MUT) as a potential biomarker of response to pembrolizumab for patients with RR-NKTCL.
a Schematic makeup of the study and the stratification of patients with RR-NKTCL accordingly to their response to pembrolizumab. b Swimmers’ plot showing the duration of responses for the 19 patients with RR-NKTCL who were treated with pembrolizumab. Tabular data showing the PD-L1 mutation status, immunohistochemical (IHC) PD-L1 positivity of tumor cells and PD-L1 stain grade (− is negative, + is weakly stained, ++ is moderately stained and + ++ is strongly stained) accompanies each corresponding NKTCL sample. c Statistical performance measures of sensitivity and precision by PD-L1MUT as a predictor for responders to pembrolizumab. d Kaplan–Meier plot comparing the overall survival of patients with PD-L1MUT and PD-L1WT tumors. e Statistical tests on various clinical features and gene-mutation between responders and non-responders were carried out and the respective -log(P value) were plotted. The vertical red line denotes the cutoff for significance at P = 0.05. f Representative images of PD-L1 IHC weakly, moderately, strongly stained images for tumors from both responders and non-responders of patients with RR-NKTCL to pembrolizumab. Percentages of tumor cells positively stained by PD-L1 antibody are in brackets. g Schematic diagram of the wild-type 9p24.1 locus and the chimeric sequence representing the PD-L1MUT detected in the tumor DNA of NKTL246. A snapshot of the aligned sequencing reads, which are soft-clipped, at the genomic breakpoint of the PD-L1MUT are shown in the ‘red’ box. h PCR-based gel validation correctly amplified the 246 bp chimeric PD-L1 sequence from the tumor (T), and not from the buccal swab (BS), water (H20). Sanger sequence validated the chimeric PD-L1 to base-pair resolution. R responder, NR non-responder, MUT mutant, WT wild type, IPI international prognostic index, ECOG eastern cooperative oncology group, n.s. not significant.
See this image and copyright information in PMC

Comment in

References

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