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  • 1
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    Characterization of genomic alterations and the significance of PI3K/mTOR pathway mutations and tumor mutational burden in non‑small cell lung cancer
    Spandidos Publications ; 2020
    In:  Oncology Reports ( 2020-03-23)
    Details
    In: Oncology Reports, Spandidos Publications, ( 2020-03-23)
    Type of Medium: Online Resource
    ISSN: 1021-335X , 1791-2431
    URL: Journal
    URL: Article
    DOI: 10.3892/or
    DOI: 10.3892/or.2020.7559
    Language: Unknown
    Publisher: Spandidos Publications
    Publication Date: 2020
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  • 2
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    Characterization of tumor mutation burden, PD-L1 and hepatitis B virus in Chinese hepatocellular carcinoma patients.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e15666-e15666
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e15666-e15666
    Abstract: e15666 Background: Hepatocellular carcinoma (HCC) has a high mortality rate and is the fourth most common cancer in China. Immunotherapy of immune checkpoint inhibitors (ICI) is a promising novel treatment strategy, but the response rate is generally low and it is not clear which patients will benefit from ICI immunotherapy. Methods: Deep sequencing targeting 450 cancer genes was done on FFPE and matched blood samples from 601 Chinese HCC patients (pts). Genomic alterations including single nucleotide variations, short and long insertions/deletions, copy number variations (CNV), gene rearrangements and fusions were analyzed. Tumor mutation burden (TMB) was measured by an algorithm developed in-house, PD-L1 expression was done by immunohistochemistry staining and Hepatitis B Virus (HBV) by target capture. Results: Patients, median age 55 years old, had TMB values in a range of 0.7 to 69.6 Muts/Mb. The 1 st Quartile, median and 3 rd Quartile TMB values were 3.8, 5.4 and 7.8 Muts/Mb, respectively. Comparing 155 pts with TMB-H (≥3 rd Quartile) to 181 TMB-L (≤1 st Quartile) pts, the mutant frequencies of TERT (49% vs 38%, p= 0.044), CTNNB1 (32% vs 11%, p 〈 0.001), LRP1B (14% vs 5%, p= 0.004) and ARID1A (12% vs 5%, p= 0.014) were higher. The mutant frequency of TP53 was lower (57% vs 68%, p= 0.035). TMB-L had younger pts (median age 50y vs 60y, p 〈 0.001) and CNV (382 vs 232, p 〈 0.001). PD-L1 expression was detected seen in 222 pts, including 152 pts of Dako 28-8 Ab and 70 pts of Dako 22C3 Ab with no preference. The PD-L1 positive rate (TPS ≥1%) was 7% and 34% in 28-8 group and 22-C3 group, respectively. Eleven pts were both TMB-H and PD-L1 positive. HBV probe signal was detected in 285 pts, 262 of which were positive (≥10 reads). TMB, PD-L1 expression and HBV were not found to be significantly correlated. Conclusions: In our study, 37% of Chinese HCC pts with PD-L1 positive or TMB-H may benefit from immunotherapy. TMB-H HCC pts were older, had more common TERT, CTNNB1, LRP1B and ARID1A mutations, and fewer TP53 mutations and CNV. In our current cohort, TMB and PD-L1, TMB and HBV, and PD-L1 expression and HBV were not correlated significantly.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e15666
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Abstract 3391: Comparison of gene copy number variations (CNV) in primary and metastatic lung cancers
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 3391-3391
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 3391-3391
    Abstract: Background: Characterization of genomic alterations that drive patient disease development is critical in cancer management. The genomic alteration and population characteristics between the primary tumors and metastases in patients with non-small cell lung cancer (NSCLC) is still unclear. Here we evaluated the frequency and distribution of all classes of genomic alterations in both primary and metastatic NSCLC by comprehensive genomic profiling approach. Methods: FFPE tumor and matched blood samples of 1135 Chinese NSCLC patients (female:male is 670: 465), including 954 primary tumors and 181 metastases, were collected for next-generation sequencing (NGS) based panel assay. Gene copy number variations (CNV) including gene amplifications and deletions, short variants, and gene fusions were assessed. Results: On average, 0.65 gene copy number variations were detected in the 181 metastatic lesions, which is higher than 0.43 CNVs per sample in the primary lesions (p value is 0.003). No significant difference was found in short variants (2.48 vs 2.31), fusions (0.27 vs 0.20) and germline mutations (0.26 vs 0.31) between the primary and metastatic NSCLC. In the top-ranked genes with copy number alterations, EGFR amplifications were detected in 11% of the primary and 15% in metastases. MET amplifications, CDKN2A/B deletions, and PMS2 deletions were more frequently found in metastatic lesions: MET (7.7% vs 1.7%, p=0.0001), CDKN2A (5.5% vs 1.5%, p=0.002), CDKN2B (5.0% vs 1.9%, p=0.0007), and PMS2 (3.9% vs 1.2%, p=0.016). Conclusions: Copy number variations are common driver mutations in NSCLC. We reported here that the prevalence of copy number variations between primary and metastatic lung cancers was different, including driver genes MET, CDKN2A/B, and PMS2. No difference was observed in terms of frequency on short variants or gene fusions in NSCLC. Citation Format: Yunfei Shi, Naiquan Mao, Xiao Ding, Jianji Guo, Gang Guo, Zheng Chen, Weiguang Gu, Lei Dai, Shiwang Wen, Hui Jia, Ziqiang Tian, Junping Shi, Taiyan Guo, Jicheng Yao, Fei Pang, Gungwei Chirn, Ming Yao. Comparison of gene copy number variations (CNV) in primary and metastatic lung cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3391.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2018-3391
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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  • 4
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    The landscape of MET mutations in Chinese biliary tract cancers.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e16652-e16652
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e16652-e16652
    Abstract: e16652 Background: Biliary tract cancers (BTCs) are malignancies with poor prognosis and limited treatment options. MET is recurrently altered in various cancers that confer susceptibility to targeted MET inhibitors. It has been reported that the MET mutation frequency is 2-7% in intrahepatic cholangiocarcinoma (ICC) and 3.7% in extrahepatic cholangiocarcinoma (ECC) in Western countries. However, the characterization of MET in Chinese BTCs are not clear. Methods: Next-generation sequencing (NGS) targeting 450 cancer genes was performed on formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matching blood samples that collected from a cohort of 926 Chinese BTC patients. Genomic alterations, including single nucleotide variations (SNV), short and long insertions/deletions (Indels), copy number variations, and gene rearrangements/fusions, were analyzed. The testing was carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Results: MET mutations were detected in 4.1% of patients with BTCs, including 5.3% in ICC, 3.4% in hilar cholangiocarcinoma (HCCA), 3.0% in ECC, and 2.6% in gallbladder cancer (GBCA). Gene amplification was the most common type of MET mutation in BTC (2.6%) compared with gene rearrangements/fusions (1.1%) and SNV (0.9%). Novel MET fusion partners, including TNS3 and TRIM4, and MET exon 14 skipping mutation, were also detected. There was no difference in tumor mutational burden (TMB) between patients with and without MET mutation (average TMB: 6.5 vs. 5.6 muts/Mb, P= 0.213). Among these BTC patients, an advanced ICC patient (performance status [PS] 3) who harbored MET gene amplification, received crizotinib as the first-line treatment. Four months later, the patient had a complete response without obvious side effects. Conclusions: To our knowledge, this is the largest BTCs cohort and the first report of MET mutation profiling in the Chinese patients. MET mutations were detected i n 4.5% BTCs, and MET inhibitors may be potential treatment options for BTC patients. All types of MET mutations, including gene amplification, SNVs, and gene fusions, were detected in BTCs, which demonstrated that NGS might be a powerful tool to detect MET mutations. Altogether, MET is a promising target in BTCs, and detection of MET mutations is important and essential for predicting the sensitivity of targeted therapy. Clinical trial information: NCT03892577 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e16652
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 5
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    Abstract 1700: Alterations of DNA damage repair genes in Chinese primary liver cancer patients and its association with tumor mutation burden
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 13_Supplement ( 2019-07-01), p. 1700-1700
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 1700-1700
    Abstract: Background: The genomic mutation features of primary liver cancer (PLC) varied from various pathology and etiology. Alterations in DNA damage repair (DDR) genes could induce genomic instability and accumulate tumor mutation burden (TMB), which was related to the efficacy of immune-checkpoint blockade treatment. However, the characteristics of DDR gene alterations and its association with TMB in PLC remain largely undefined. Method: We enrolled 357 Chinese PLC patients as training cohort and used the TCGA-LIHC data of 373 hepatocellular cancer patients as validation cohort. FFPE tumor tissues and matched blood samples were collected from these Chinese patients for next-generation-sequencing (NGS)-based 450 genes panel assay, which contains 35 DDR genes. All histological diagnoses were confirmed by independent pathologists. Correlation of the DDR pathway genes alterations with TMB was assessed by multiple linear regression model using R package “nlme”. The receiver operating characteristic (ROC) curve was applied to determine the diagnostic efficiency of DDR pathway genes for TMB high (which was defined as the top quantile) using R package “pROC”. Results: The training cohort of Chinese PLC patients included 282 males and 75 females with the mean age of 56.3 years old. The pathologic subtypes include 214 hepatocellular carcinoma (HCC), 122 intrahepatic cholangiocarcinoma (ICC) and 21 mixed hepato-cholangiocellular carcinoma (H-ChC). There are 25.8% (92/357) patients had at least one DDR gene alteration. The DDR mutation rate showed no significant differences among three subtypes of PLC (HCC vs ICC vs H-Chc: 22.9% (49/214) vs 30.3% (37/122) vs 28.6% (6/21), P=0.311). In addition, 16.3% (15/92) of the patients with DDR gene mutations have germline variations. The TMB in HCC patients was significantly higher than that in ICC patients but not in H-ChC patients (median TMB for HCC, ICC and H-ChC was 5.4, 3.1, and 3.9 Muts/Mb, Kruskal-Wallis test, P & lt;0.001). Importantly, PLC patients with DDR gene mutations had significantly higher TMB compared to patients without DDR gene mutation (6.2 vs 3.9 Muts/Mb, P & lt;0.001), which was further validated in TCGA-LIHC data (95 vs 64 mutations, P & lt;0.001). The patients with germline DDR gene mutations had significant lower TMB compared with patients with somatic DDR gene mutations (3.1 vs 6.3 Muts/Mb, Wilcox test, P=0.041). We further defined 3 subtypes of DDR pathways (BER, FA and MMR) that significantly correlated with TMB in the training cohort, which exhibited diagnostic efficiency in distinguishing TMB-high or TMB-low PLC in TCGA-LIHC dataset (AUC: 0.67). Conclusion: DDR gene alterations were significantly positively associated with TMB in PLC. Mutations occurred in BER, FA or MMR pathways indicated higher TMB in PLC, which have the potential to serve as markers to predict the TMB level to guide the immune-checkpoint inhibitor therapy. Citation Format: Jianzhen Lin, Honglin Guo, Junping Shi, Xu Yang, Yan Jiang, Yi Bai, Junyu Long, Dongxu Wang, Jin Bian, Ming Yao, Kai Wang, Haitao Zhao. Alterations of DNA damage repair genes in Chinese primary liver cancer patients and its association with tumor mutation burden [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1700.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2019-1700
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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  • 6
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    Abstract 2508: Genomic alterations of BRCA1/2 genes in Chinese solid tumor patients
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 13_Supplement ( 2019-07-01), p. 2508-2508
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 2508-2508
    Abstract: Background: BRCA1 and BRCA2 are tumor suppressor genes that play an important role in DNA repair pathways. Germline mutations in BRCA1 and BRCA2 contribute to a significant number of familial and hereditary breast and/or ovarian cancers. Additionally, BRCA 1/2 alterations induce sensitivity to poly ADP ribose polymerase inhibitors (PARPi). Therefore, the detection of BRCA 1/2 mutations in solid tumor patients is essential to predict the sensitivity to PARPi therapy. Methods: FFPE tumor and matched blood samples of 5269 Chinese patients with solid tumor were collected for next generation sequencing (NGS) based assay. Genomic alterations including single nucleotide variations (SNV), short and long insertions/deletions (Indel), copy number variations (CNV) and gene rearrangements and fusions in selected genes were assessed. Results: Three hundred patients with BRCA1/2 mutations were identified in 5269 Chinese patients with solid tumor. The patients included 177 males and 123 females with a median age of 58. Highest yields of BRCA1/2 mutations were found in patients with ovarian (24.5%) and breast (12.3%) cancers. BRCA1/2 mutations were also identified in gastric cancer (8.9%), cholangiocarcinoma (8.8%), colorectal cancer (7.1%), esophageal cancer (6.1%), gallbladder cancer (5.1%), lung cancer (4.7%), soft tissue tumor (4.1%) and pancreatic cancer (4.0%). SNVs and short Indels (84.9%) were the most common variant types of BRCA1/2, while the percentages of gene rearrangements and fusions, CNV and long Indels were 12.0%, 1.6% and 1.5%, respectively. Among patients with BRCA1/2 mutations, 224 (74.7%) patients harbored somatic mutations, 73 (24.3%) patients harbored germline mutations, 3 (1.0%) patients harbored both somatic and germline mutations. Interestingly, all of the variant types of germline mutations were SNVs and short Indels. The mutation sites were distributed in the full length of BRCA1/2 genes. No hot spot mutation was observed. Conclusions: Our data revealed that BRCA1/2 mutations occurred in 5.7% of Chinese patients with solid tumor. NGS targeted sequencing provides comprehensive and accurate information of BRCA1/2 mutations. Beyond ovarian and breast cancers, BRCA1/2 mutations could be detected in other solid tumors, which suggests potential clinical benefits from PARPi therapy. Citation Format: Junjian Wang, Lingxiang Liu, Bin Ni, Xiaoqian Chen, Ling Li, Junping Shi, Jierong Chen, Ming Yao. Genomic alterations of BRCA1/2 genes in Chinese solid tumor patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2508.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2019-2508
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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    detail.hit.zdb_id: 1432-1
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  • 7
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    Abstract 3428: The landscape of germline mutations in Chinese patients with solid tumor
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 13_Supplement ( 2019-07-01), p. 3428-3428
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 3428-3428
    Abstract: Background: Germline mutations harbored by cancer patients can be passed from parents on to offspring, which increases the tumor risk in offspring as well. Therefore, investigating the germline mutations in cancer patients has important clinical implications for treatment selection and familial cancer risk assessment. Methods: FFPE tumor and matched blood samples were collected from 3645 Chinese patients with solid tumors for next generation sequencing analysis. The NGS panel targeted 450 cancer genes, 47 of these genes were tumor inheritance susceptibility genes that were mentioned by NCCN guidelines. Genomic alterations including single nucleotide variations (SNV), short and long insertions/deletions (Indel), copy number variations (CNV) and gene rearrangements and fusions were assessed. Results:Germline mutations were identified in 241 of 3645 Chinese patients with solid tumor (6.6%). The patients with germline mutations included 137 males and 104 females with a median age of 54. Tumor types with higher frequency of germline mutations were: ovarian cancer (22.0%), breast cancer (13.4%), pancreatic cancer (9.9%), cholangiocarcinoma (8.6%), small intestinal cancer (8.6%), colorectal cancer (8.6%), soft tissue sarcoma (6.3%), uterine Cancer (5.9%), gastric cancer (5.8%) and bone cancer (5.1%). The distribution of germline mutations were 14.1% in BRCA1, 13.7% in BRCA2, 10.8% in SPINK1, 9.1% in ATM, 5.8% in RAD50, 4.6% in PALB2, 3.7% in BARD1 and FANCA, 3.3% in MSH6 and 2.9% in MLH1, respectively. The types of germline mutations were SNVs and short Indels, but no long Indels, CNV, gene rearrangements or fusions were observed. The percentage of patients with a family history was 27.4%, without family history was 52.7%, unknown was 19.9%. Conclusions:Our data revealed that germline mutations occurred in 6.6% of Chinese solid tumor patients. Gynecological tumor, gastrointestinal tumor, bone and soft tissue tumor are the most common types of tumors that harbored germline mutations. The most common mutant genes were HRD (64.5%) and MMR (10.5%) related genes. More than 50% patients with germline mutations had no family history, which suggests the importance of germline mutations detection for all solid tumor patients to verify if there is a risk of genetic transmission to offspring. NGS based panel sequencing showed the advantage of identifying solid tumor patients with germline mutations, and provided the information of familial cancer risk assessment and guided the precise cancer treatment options. Citation Format: Juming Li, Yongzhong Wei, Xiaoqian Chen, Angen Liu, Junping Shi, Jinwei Hu, Ming Yao. The landscape of germline mutations in Chinese patients with solid tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3428.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2019-3428
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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  • 8
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    Next-Generation Sequencing Assisted in Establishing the Diagnosis and Treatment for a Chinese Patient With Breast and Lung Multiple Primary Malignancies
    Elsevier BV ; 2018
    In:  Journal of Thoracic Oncology Vol. 13, No. 7 ( 2018-07), p. e109-e111
    Details
    In: Journal of Thoracic Oncology, Elsevier BV, Vol. 13, No. 7 ( 2018-07), p. e109-e111
    Type of Medium: Online Resource
    ISSN: 1556-0864
    URL: Article
    DOI: 10.1016/j.jtho.2018.03.019
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2223437-8
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  • 9
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    Effectiveness of EGFR-TKIs in a Patient with Lung Adenocarcinoma Harboring an EGFR-RAD51 Fusion
    Oxford University Press (OUP) ; 2019
    In:  The Oncologist Vol. 24, No. 8 ( 2019-08-01), p. 1027-1030
    Details
    In: The Oncologist, Oxford University Press (OUP), Vol. 24, No. 8 ( 2019-08-01), p. 1027-1030
    Abstract: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) have become the first choice for patients with sensitive mutations and have significantly improved prognosis. EGFR exon 19 deletions and L858R mutation in exon 21 are the most common sensitive mutations in lung adenocarcinoma. With advances in detection technology, some rare variants of EGFR have been detected, including EGFR kinase domain duplications and EGFR fusions. Only a few reports have revealed the effectiveness of EGFR-TKIs in patients with these rare variants. In this study, we report a case of EGFR-RAD51 fusion in lung adenocarcinoma that showed a response to icotinib; these findings provide additional support for the use of EGFR-TKIs for patients with these atypical variants. Key Points A young patient with lung adenocarcinoma harboring a rare EGFR-RAD51 fusion who responded to icotinib with a PFS of longer than 15 months. All reported EGFR-RAD51 fusions have the same breakpoints and show responses to EGFR-TKIs including icotinib, except for one patient who responded to chemotherapy. Although EGFR fusion is a rare EGFR variant type, the efficacy of EGFR-TKIs suggests the necessity for new detection technology, such as NGS, for patients with lung adenocarcinoma. The clinical usage of NGS could maximize the benefits of precision medicine in patients with cancer. The current case provides new evidence for the efficacy of icotinib in patients with the rare EGFR-RAD51 fusion and EGFR-activating mutations.
    Type of Medium: Online Resource
    ISSN: 1083-7159 , 1549-490X
    URL: Article
    DOI: 10.1634/theoncologist.2018-0732
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2023829-0
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  • 10
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    Abstract 3548: Loss of heterozygosity (LOH) as a candidate biomarker of PARP inhibitor sensitivity in Chinese solid tumor patients
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 16_Supplement ( 2020-08-15), p. 3548-3548
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 3548-3548
    Abstract: Background: Poly (ADP-ribose) polymerase (PARP) plays a vital role in the repair of single-strand DNA breaks through the base excision repair pathway. Several PARP inhibitor approved for advanced BRCA-mutated (BRCAm) ovarian cancer. PARP inhibitors may benefit patients whose tumors are dysfunctional in DNA repair mechanisms unrelated to BRCA1/2. Here we descript the clinical application of LOH score as a candidate biomarker to predicate therapeutic response of PARP inhibitor in Chinese solid tumor patients. Methods: Formalin fixed paraffin embedded (FFPE) samples of 16 Chinese solid tumor patients were collected for next-generation sequencing (NGS) based 450 genes panel assay. Genomic alterations including single base substitution, short and long insertions/deletions, copy number variations, gene fusions and rearrangement were assessed. Loss of heterozygosity (LOH) status, Microsatellite stable (MSS) status and TMB (tumor mutational burden) were also acquired by an NGS algorithm. Results: There are 16 patients were analyzed in this retrospective study that most patients having advanced disease stage, Including 9 males and 7 females. The median age is 64 (range, 40-72) years old. The tumor type of these patients including Hepatocellular carcinoma (N=3), Cholangiocarcinoma (N=7), Breast cancer (N=2), Prostate cancer (N=2), Lymphoepithelioma like carcinoma (N=1) and Gallbladder adenocarcinoma (N=1). All 16 patients were treated with PARP inhibitor (Olaparib) including 14 patients harboring BRCA1/2 mutation. 15 patients were evaluable, OS (overall survival) time was calculated until abstract publish. 1 patients achieved complete response (CR), 4 patients achieved partial response (PR), 9 had stable disease (SD) and 1 had progressive disease (PD). Two patients with BRCA wild type achieved SD and the OS time was 13 and 37 months, respectively. LOH status was evaluated all tumors, 25% (4/16) of patients would be considered as having high LOH (LOH-H), including 2 patients without BRCA mutation. 75% (12/16) patients considered as having low LOH (LOH-L). LOH-high group has a longer OS time (P=0.056), median OS time of LOH-H group (N=4) is 25 month (range, 4-42) and LOH-L group (N=11) is 6 month (range, 2-23). Also we explored the association between TMB and OS, identified TMB-H patients (N=6) morel likely has a longer OS (median OS, 11.5 VS 5 month, P=0.017). Conclusion: In patients with advanced solid cancer, High LOH status was associated with good therapeutic response of PARP inhibitor. LOH status may become a potential indicator for the treatment of PARP inhibitors. Due to the limitations of the number and clinical baseline of patients, the results may require further research and validation. Citation Format: Jinwei Hu, Shuirong Zhang, Kai You, Lijuan Chen, Peng Zhang, Junping Shi, Ming Yao, Mo Wang, Kai Wang. Loss of heterozygosity (LOH) as a candidate biomarker of PARP inhibitor sensitivity in Chinese solid tumor patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3548.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2020-3548
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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