Genomic comparison between cerebrospinal fluid and primary tumor revealed the genetic events associated with brain metastasis in lung adenocarcinoma

Deng, Zhiyong; Cui, Liang; Li, Pansong; Ren, Nianjun; Zhong, Zhe; Tang, Zhi; Wang, Lei; Gong, Jianwu; Cheng, Haofeng; Guan, Yanfang; Yi, Xin; Xia, Xuefeng; Zhou, Rongrong; He, Zhengwen

doi:10.1038/s41419-021-04223-4

Cited by 16 publications

(11 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Up to now,no previous article reports the TMB of lung cancer of lemptomenigel metastasis.The mean TMB of 8.4 mutations/Mb in our study was higher than previous report of 5 mutations/Mb of EGFR mutant CSF [31].12 cases' TMB was more than 10 mutations/Mb.However in our study,there was no signi cant difference of TMB among patients received TKI or not.As for EGFR sensitive mutation,TMB of patients harboring EGFR 21L85R was higher than patients harboring EGFR 19del,while the difference wasn't signi cant.PD-L1 expression and tumor mutational burden (TMB) are the most studied and validated predictive biomarkers of response to ICIs [32]. TMB appeared to be associated with clinical bene t to PD-1/PD-L1 antibodies, potentially relating to an increase in neoantigen speci c T-cell activity [33].Although EGFR positive NSCLC patients do not derive a signi cant bene t from ICIs therapy [34,35],Orient 31 demonstrated Sintilimab with antivascular plus chemotherapy prolonged PFS (6.9 vs 4.3months ) in patients with EGFR mutated nonsquamous NSCLC who progressed after EGFR-TKI therapy than chemothepy.Some patients with NSCLC having LM especi cally, those in the NCCN LM good prognosis group do bene t from ICI treatment [36].As for those LM patients especially those with relatively high TMB, ICIs combined with other agents such as chemotherapy or angiogenesis inhibitor maybe a therapeutic strategy when they progressed on EGFR-TKI.…”

Section: Discussioncontrasting

confidence: 81%

Genotyping of cerebrospinal fluid for leptomeningeal metastases in EGFR-mutated lung cancer

Geng

Niu

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Leptomeningeal metastasis (LM) is a detrimental complication of advanced lung cancer, more frequently occurring in patients harboring epidermal growth factor receptor (EGFR) mutation. Due to limited access to the leptomeningeal lesion, we explored the potential role of cerebrospinal fluid (CSF) as a source for liquid biopsy in LM patients with EGFR mutation.Materials and methods: The CSF samples from Lung cancer patients with LM were collected between June 2021 and August 2018 at First Affiliated Hospital of Zhengzhou University. Next-generation sequencing was performed to detect the mutations in EGFR genes, overall 38 patients detected with EGFR mutations were finally enrolled in further retrospectively clinical analyses.Results: CSF samples of 38 lung patients with LM harboring EGFR mutation were enrolled in this study.we found 20 cases of L858R of exon 21 and 14 cases of exon 19 deletion.Other EGFR mutations included EGFR exon 20 insertion(n=1),EGFR G719A of exon 18 (n=1) ,EGFR G719S of exon 18 (n=1), EGFR S768I of exon 20 and G719C of exon 18(n=1).CSF samples from 6 patients were collected before prescribing them TKIs.The most frequently detected concurrent genes in CSF was TP53 missense mutation(50%).CSF of 10 patients were obtained after failure to 1st TKI.The most frequently detected concurrent genes in CSF were TP53 missense mutation(40%,n=4),EGFR copy number amplification (40%,n=4) and NKX2-1 copy number gain(30.0%,n=3).Acquired resistance to 1st TKI of T790M mutation was detected in two patients. Similarly, the CSF samples from 22 patients were collected during their 3rd TKI therapy and the TP53 missense mutation was detected in 31.8% of patients followed by EGFR amplification (22.7%), STK11 deletions (18.2%) and MYC amplification (18.2%), while two patients harbored T790M mutation. Known mechanisms of acquired resistance to EGFR- 3rd TKIs were identified in 31.8% of cases. C797S and C797G mutation was found in three patients.Possible EGFR-independent resistant mechanism included PIK3CA missense mutation(4.5%),MET amplification(4.5%),CDK4 amplification(4.5%) and RET gene fusion(4.5%).In the 38 cases , average TMB was 8.4mutations/Mb (median 6.9 , range 1.1-23.83mutations/Mb) ,12 cases with more than 10 mutations/Mb. There were no significant difference of CSF TMB among the three group of patients who hadn’t received TKI, progressed on 1st TKI and progressed on 3rd TKI.Conclusion: CSF cfDNA provided comprehensive profiles of driver and resistance genes of lung cancer with LM harboring EGFR mutation, supporting the importance of CSF cfDNA as a liquid biopsy medium and guiding the choice of anti-tumor drugs.

show abstract

Section: Discussioncontrasting

confidence: 81%

Genotyping of cerebrospinal fluid for leptomeningeal metastases in EGFR-mutated lung cancer

Geng

Niu

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Of note, enrichment in TP53 alterations has been observed in BrM from breast carcinoma, whereas enrichment in EGFR and CDKN2A alterations has been found in BrM from lung adenocarcinoma. 53 , 54 …”

Section: Discussionmentioning

confidence: 99%

“…Finally, alterations in other GEA-associated genes were seen at high frequency in our cohort, including TP53 , EGFR , CDKN2A , SMAD4 , and ARID1A , but were not significantly enriched among BrM samples specifically. Of note, enrichment in TP53 alterations has been observed in BrM from breast carcinoma, whereas enrichment in EGFR and CDKN2A alterations has been found in BrM from lung adenocarcinoma …”

Section: Discussionmentioning

confidence: 99%

Outcomes and Molecular Features of Brain Metastasis in Gastroesophageal Adenocarcinoma

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The SNV count was defined as the total number of SNV events per sample. The Fisher’s t -test was performed to compare differences between various groups ( 14 ).…”

Section: Methodsmentioning

confidence: 99%

The ctDNA-based postoperative molecular residual disease status in different subtypes of early-stage breast cancer

Yang¹,

Zhang²,

Li³

et al. 2022

Gland Surg

View full text Add to dashboard Cite

Background: Breast cancer is a highly heterogeneous disease. Early-stage, non-metastatic breast cancer is considered curable after definitive treatment. Early detection of tumor recurrence and metastasis through sensitive biomarkers is helpful for guiding clinical decision-making and early intervention in second-line treatment, which could improve patient prognosis and survival.Methods: In this real-world study, we retrospectively analyzed 82 patients with stages I to III breast cancer who had been analyzed by molecular residual disease (MRD) assay. A total of 82 tumor tissues and 224 peripheral blood samples were collected and detected by next-generation sequencing (NGS) based on a 1,021-gene panel in this study.Results: MRD positivity was detected in 18 of 82 patients (22.0%). The hormone receptor−/human epidermal growth factor receptor 2+ (HR−/HER2+) subgroup had the highest postoperative MRD detection rate at 30.8% (4/13). The BRCA2 and SLX4 genes were significantly enriched in all patients in the MRD positive group and FGFR1 amplification was significantly enriched in the MRD negative group with HR+/ HER2−. The number of single nucleotide variants (SNVs) in tissue samples of MRD-positive patients was higher than that of MRD-negative patients (11.94 vs. 8.50 SNVs/sample). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that there was a similar biological function of the tumormutated genes in the 2 MRD status groups.Conclusions: This real-world study confirmed that patient samples of primary tumor tissue with different MRD status and molecular subtypes had differential genetic features, which may be used to predict patients at high risk for recurrence.

show abstract

Genomic comparison between cerebrospinal fluid and primary tumor revealed the genetic events associated with brain metastasis in lung adenocarcinoma

Cited by 16 publications

References 55 publications

Genotyping of cerebrospinal fluid for leptomeningeal metastases in EGFR-mutated lung cancer

Genotyping of cerebrospinal fluid for leptomeningeal metastases in EGFR-mutated lung cancer

Outcomes and Molecular Features of Brain Metastasis in Gastroesophageal Adenocarcinoma

The ctDNA-based postoperative molecular residual disease status in different subtypes of early-stage breast cancer

Contact Info

Product

Resources

About