In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e17531-e17531
Abstract:
e17531 Background: Prostate cancer with microsatellite instability-high (MSI-H) is identified as a distinct genotype that potentially benefit from immune checkpoint inhibitors. But the incidence and genomic profiling of microsatellite instability haven’t been well characterized in Chinese prostate cancer patients. Methods: Tumor tissue and matched blood sample from 241 Chinese prostate cancer patients were analyzed with targeted next-generation sequencing covering whole exon of 381 or 90 genes and 100 microsatellite loci. Tumor mutation burden (TMB), defined by non-silent somatic mutation counts in coding region per megabase (Mb), was calculated in tumors sequenced by 381-gene panel with coding region of 1.12Mb. Results: 7 patients (2.90%) were identified as MSI-H in overall population. Somatic or germline alterations of mismatch repair genes were detected in 5 of the 7 patients, including 2 MSH2 germline mutations, 2 MSH6 somatic mutations, 1 MSH2 somatic mutation, 1 PMS2 somatic mutation and 1 MLH3 somatic mutation. In MSI-H tumors, alterations in KMT2C (6/7), EGFR (5/7), KMT2D (5/7), JAK1 (5/7), PTEN (4/7), TP53 (3/7), ZFHX3 (3/7) and SPOP (3/7) were common. AR ligand binding domain was mutated in 3 of 7 patients, while no AR amplification was detected in MSI-H tumors. In 121 tumors sequenced by 381-gene panel, median TMB was 3.23 mutations/Mb. Median TMB was significantly higher in MSI-H tumors compared with MSS tumors (median TMB, 13.71 mutations/Mb versus 2.93 mutations/Mb, P 〈 0.001). Median counts of single nucleotide variants (SNVs) and insertion-deletions (Indels) were 13 and 10 in MSI-H tumors that were also higher than that of MSS tumors with median SNVs and Indels of 2 (P = 0.004) and 1 (P 〈 0.001), respectively. Conclusions: 2.9% patients were identified as MSI-H in Chinese prostate patients. MSI-H was associated with higher TMB, SNVs and Indels. Targeted next-generation sequencing is a practical tool for prostate cancer genotyping and treatment decision-making.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.e17531
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2020
detail.hit.zdb_id:
2005181-5
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