Abstract 2245: Analysis of PALB2 in Chinese hepato-bilio-pancreaticcancer and correlation with immunogenic biomarker
Authors: Ou Li , Zheng Yating , Xie Wenzhuan , Huang Mengli 
Published: July 2021

Background: The role of germline PALB2 variants as a major susceptibility gene has been reported in breast, ovarian, and pancreatic cancers. But the PALB2 characteristics in hepato-bilio-pancreatic cancers, which include hepatic carcinoma (LIHC), biliary tract cancer (BTC), and pancreatic Carcinoma (PAAD), and its correlation with immunogenic marker was unknown.

Methods: Tumor tissue samples from Chinese hepato-bilio-pancreatic cancer patients were analyzed using next generation sequencing (panel on 381/733-gene). TMB was defined as total number of somatic non-synonymous mutations in coding region. MSI was evaluated by NGS of 500 known MSI loci. PD-L1 expression was evaluated using immunohistochemistry (SP142).

Results: The PALB2 mutation frequency in hepato-bilio-pancreatic cancers was 4.19% (190/4531), among 4.49% (93/2073) of LIHC, 4.17% (63/1511) of BTC, and 3.59% (34/947) of PAAD. The germline PALB2 mutation (PALB2gmut) and somatic PALB2 mutation (PALB2smut) frequency was 2.67% (121/4531) and 1.52% (69/4531) in hepato-bilio-pancreatic cancers, among 2.41% (50/2073) and 2.07% (43/2073) of LIHC, 3.04% (46/1511) and 1.13% (17/1511) of BTC, and 2.64% (25/947) and 0.95% (9/947) of PAAD. The mutation frequency of TP53 was highest in LIHC with PALB2gmut (64%), which is consistent with LIHC patients with PALB2smut (72%). In BTC patients, the most frequently mutated gene was TP53 (54%) in patients with PALB2gmut and MGMT (65%) in patients with PALB2smut. The gene with the highest frequency of mutations in PAAD patients with PALB2gmut is KRAS (84%), which is consistent with PAAD patients with PALB2smut (89%). There was no difference in PD-L1 expression among PALB2gmut, PALB2smut and PALB wild-type (PALB2wt) in any of the tumors mentioned above (P&gt;0.05). In LIHC, PALB2smut has a higher TMB than PALB2wt (P=0.0003). The same phenomenon has also been observed in BTC (P=0.0014) and PAAD (P=0.0017). But there was no significant difference on TMB between PALB2gmut and PALB2wt (P=0.45 of LIHC, P= 0.21 of BTC, P=0.42 of PAAD). In PAAD, the ratio of MSI-H in PALB2smut patients was significantly higher than that in PALB2wt patients (P&lt;0.001), while in LIHC and BTC, the ratio of MSI-H in PALB2smut showed no significant benefit, but showed a higher trend (P=0.074, P=0.095). However, in all three types of tumors, there was no significant difference on MSI-H ratio between PALB2gmut and PALB2wt (P&gt;0.5).

Conclusions: We found that PALBgmut was more frequent in all three tumors. However, PALBsmut are associated with higher TMB and have a higher MSI-H ratio. These findings provide a theoretical basis for the future clinical study of PALB2 in predicting the efficacy of immunotherapy and PARP inhibitor therapy in Chinese hepato-bilio-pancreatic cancer patients.

Citation Format: Li Ou, Yating Zheng, Wenzhuan Xie, Mengli Huang. Analysis of PALB2 in Chinese hepato-bilio-pancreaticcancer and correlation with immunogenic biomarker [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2245.