Research ArticleOriginal Article

The mutational pattern of homologous recombination (HR)-associated genes and its relevance to the immunotherapeutic response in gastric cancer

Yue Fan, Haifeng Ying, Xueying Wu, Huan Chen, Ying Hu, Henghui Zhang, Lijia Wu, Ying Yang, Beibei Mao and Lan Zheng
Cancer Biology & Medicine November 2020, 17 (4) 1002-1013; DOI: https://doi.org/10.20892/j.issn.2095-3941.2020.0089

References

  1. ↵
    2. Bray F,
    3. Ferlay J,
    4. Soerjomataram I,
    5. Siegel RL,
    6. Torre LA,
    7. Jemal A.
    Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68: 394–424.
    OpenUrlCrossRefPubMed
  2. ↵
    2. Strong VE,
    3. Wu AW,
    4. Selby LV,
    5. Gonen M,
    6. Hsu M,
    7. Song KY, et al.
    Differences in gastric cancer survival between the U.S. and China. J Surg Oncol. 2015; 112: 31–7.
    OpenUrlCrossRefPubMed
  3. ↵
    2. Bonelli P,
    3. Borrelli A,
    4. Tuccillo FM,
    5. Silvestro L,
    6. Palaia R,
    7. Buonaguro FM.
    Precision medicine in gastric cancer. World J Gastrointest Oncol. 2019; 11: 804–29.
    OpenUrlCrossRef
  4. ↵
    2. Shitara K,
    3. Ozguroglu M,
    4. Bang YJ,
    5. Di Bartolomeo M,
    6. Mandala M,
    7. Ryu MH, et al.
    Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018; 392: 123–33.
    OpenUrlCrossRefPubMed
  5. ↵
    2. Morse CB,
    3. Toukatly MN,
    4. Kilgore MR,
    5. Agnew KJ,
    6. Bernards SS,
    7. Norquist BM, et al.
    Tumor infiltrating lymphocytes and homologous recombination deficiency are independently associated with improved survival in ovarian carcinoma. Gynecol Oncol. 2019; 153: 217–22.
    OpenUrlPubMed
  6. ↵
    2. Venkitaraman AR.
    Linking the cellular functions of BRCA genes to cancer pathogenesis and treatment. Annu Rev Pathol. 2009; 4: 461–87.
    OpenUrlCrossRefPubMedWeb of Science
  7. ↵
    2. Ang YLE,
    3. Tan DSP.
    Development of PARP inhibitors in gynecological malignancies. Curr Probl Cancer. 2017; 41: 273–86.
    OpenUrl
    2. Chartron E,
    3. Theillet C,
    4. Guiu S,
    5. Jacot W.
    Targeting homologous repair deficiency in breast and ovarian cancers: biological pathways, preclinical and clinical data. Crit Rev Oncol Hematol. 2019; 133: 58–73.
    OpenUrl
  9. ↵
    2. Pilie PG,
    3. Gay CM,
    4. Byers LA,
    5. O’Connor MJ,
    6. Yap TA.
    PARP inhibitors: extending benefit beyond BRCA-mutant cancers. Clin Cancer Res. 2019; 25: 3759–71.
    OpenUrlAbstract/FREE Full Text
  10. ↵
    2. Goodall J,
    3. Mateo J,
    4. Yuan W,
    5. Mossop H,
    6. Porta N,
    7. Miranda S, et al.
    Circulating cell-free DNA to guide prostate cancer treatment with PARP inhibition. Cancer Discov. 2017; 7: 1006–17.
    OpenUrlAbstract/FREE Full Text
  11. ↵
    2. Tao Y,
    3. Mei Y,
    4. Ying R,
    5. Chen S,
    6. Wei Z.
    The ATM rs189037 G>A polymorphism is associated with the risk and prognosis of gastric cancer in Chinese individuals: a case–control study. Gene. 2020; 741: 144578.
    OpenUrl
  12. ↵
    2. Buisson R,
    3. Niraj J,
    4. Rodrigue A,
    5. Ho CK,
    6. Kreuzer J,
    7. Foo TK, et al.
    Coupling of homologous recombination and the checkpoint by ATR. Mol Cell. 2017; 65: 336–46.
    OpenUrlCrossRefPubMed
  13. ↵
    2. Juhasz S,
    3. Elbakry A,
    4. Mathes A,
    5. Lobrich M.
    ATRX Promotes DNA repair synthesis and sister chromatid exchange during homologous recombination. Mol Cell. 2018; 71: 11–24 e7.
    OpenUrlCrossRef
  14. ↵
    2. Lord CJ,
    3. Ashworth A.
    PARP inhibitors: synthetic lethality in the clinic. Sci. 2017; 355: 1152–8.
    OpenUrlAbstract/FREE Full Text
  15. ↵
    2. Mani C,
    3. Jonnalagadda S,
    4. Lingareddy J,
    5. Awasthi S,
    6. Gmeiner WH,
    7. Palle K.
    Prexasertib treatment induces homologous recombination deficiency and synergizes with olaparib in triple-negative breast cancer cells. Breast Cancer Res. 2019; 21: 104.
    OpenUrl
  16. ↵
    2. Witjes WP.
    Re: DNA-repair defects and olaparib in metastatic prostate cancer. Eur Urol. 2016; 70: 204–5.
    OpenUrl
  17. ↵
    2. Kondrashova O,
    3. Nguyen M,
    4. Shield-Artin K,
    5. Tinker AV,
    6. Teng NNH,
    7. Harrell MI, et al.
    Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor Rucaparib in high-grade ovarian carcinoma. Cancer Discov. 2017; 7: 984–98.
    OpenUrlAbstract/FREE Full Text
  18. ↵
    2. Thorsson V,
    3. Gibbs DL,
    4. Brown SD,
    5. Wolf D,
    6. Bortone DS,
    7. Ou Yang TH, et al.
    The immune landscape of cancer. Immunity. 2018; 48: 812–30 e14.
    OpenUrlCrossRefPubMed
    2. Hoadley KA,
    3. Yau C,
    4. Hinoue T,
    5. Wolf DM,
    6. Lazar AJ,
    7. Drill E, et al.
    Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer. Cell. 2018; 173: 291–304 e6.
    OpenUrlCrossRefPubMed
    2. Bonneville R,
    3. Krook MA,
    4. Kautto EA,
    5. Miya J,
    6. Wing MR,
    7. Chen HZ, et al.
    Landscape of microsatellite instability across 39 cancer types. JCO Precis Oncol. 2017; 2017: 1–15.
    OpenUrl
  21. ↵
    2. Davoli T,
    3. Uno H,
    4. Wooten EC,
    5. Elledge SJ.
    Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy. Sci. 2017; 355: eaaf8399.
  22. ↵
    2. Turajlic S,
    3. Litchfield K,
    4. Xu H,
    5. Rosenthal R,
    6. McGranahan N,
    7. Reading JL, et al.
    Insertion-and-deletion-derived tumour-specific neoantigens and the immunogenic phenotype: a pan-cancer analysis. Lancet Oncol. 2017; 18: 1009–21.
    OpenUrlCrossRefPubMed
  23. ↵
    2. Newman AM,
    3. Liu CL,
    4. Green MR,
    5. Gentles AJ,
    6. Feng W,
    7. Xu Y, et al.
    Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015; 12: 453–7.
    OpenUrlCrossRefPubMed
  24. ↵
    2. Rooney MS,
    3. Shukla SA,
    4. Wu CJ,
    5. Getz G,
    6. Hacohen N.
    Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell. 2015; 160: 48–61.
    OpenUrlCrossRefPubMedWeb of Science
  25. ↵
    2. Ayers M,
    3. Lunceford J,
    4. Nebozhyn M,
    5. Murphy E,
    6. Loboda A,
    7. Kaufman DR, et al.
    IFN-gamma-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest. 2017; 127: 2930–40.
    OpenUrlCrossRefPubMed
  26. ↵
    2. Samstein RM,
    3. Lee CH,
    4. Shoushtari AN,
    5. Hellmann MD,
    6. Shen R,
    7. Janjigian YY, et al.
    Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019; 51: 202–6.
    OpenUrlCrossRefPubMed
  27. ↵
    2. Sahasrabudhe R,
    3. Lott P,
    4. Bohorquez M,
    5. Toal T,
    6. Estrada AP,
    7. Suarez JJ, et al.
    Germline mutations in PALB2, BRCA1, and RAD51C, which regulate DNA recombination repair, in patients with gastric cancer. Gastroenterology. 2017; 152: 983–6 e6.
    OpenUrl
  28. ↵
    2. Mateo J,
    3. Carreira S,
    4. Sandhu S,
    5. Miranda S,
    6. Mossop H,
    7. Perez-Lopez R, et al.
    DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med. 2015; 373: 1697–708.
    OpenUrlCrossRefPubMed
    2. Coleman RL,
    3. Oza AM,
    4. Lorusso D,
    5. Aghajanian C,
    6. Oaknin A,
    7. Dean A, et al.
    Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017; 390: 1949–61.
    OpenUrlCrossRefPubMed
  30. ↵
    2. Swisher EM,
    3. Lin KK,
    4. Oza AM,
    5. Scott CL,
    6. Giordano H,
    7. Sun J, et al.
    Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2017; 18: 75–87.
    OpenUrlCrossRefPubMed
  31. ↵
    2. Wang F,
    3. Wei XL,
    4. Wang FH,
    5. Xu N,
    6. Shen L,
    7. Dai GH, et al.
    Safety, efficacy and tumor mutational burden as a biomarker of overall survival benefit in chemo-refractory gastric cancer treated with toripalimab, a PD-1 antibody in phase Ib/II clinical trial NCT02915432. Ann Oncol. 2019; 30: 1479–86.
    OpenUrlPubMed
  32. ↵
    2. O’Kane GM,
    3. Connor AA,
    4. Gallinger S.
    Characterization, detection, and treatment approaches for homologous recombination deficiency in cancer. Trends Mol Med. 2017; 23: 1121–37.
    OpenUrlCrossRef
  33. ↵
    2. Fuchs CS,
    3. Doi T,
    4. Jang RW,
    5. Muro K,
    6. Satoh T,
    7. Machado M, et al.
    Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol. 2018; 4: e180013.
  34. ↵
    2. Goodman AM,
    3. Sokol ES,
    4. Frampton GM,
    5. Lippman SM,
    6. Kurzrock R.
    Microsatellite-stable tumors with high mutational burden benefit from immunotherapy. Cancer Immunol Res. 2019; 7: 1570–3.
    OpenUrlAbstract/FREE Full Text
  35. ↵
    2. Gong L-P,
    3. Chen J-N,
    4. Xiao L,
    5. He Q,
    6. Feng Z-Y,
    7. Zhang Z-G, et al.
    The implication of tumor-infiltrating lymphocytes in Epstein-Barr virus–associated gastric carcinoma. Hum Pathol. 2019; 85: 82–91.
    OpenUrl
  36. ↵
    2. Scherrenburg J,
    3. Piriou ERWAN,
    4. Nanlohy NM,
    5. van Baarle D.
    Detailed analysis of EpsteinBarr virus-specific CD4and CD8T cell responses during infectious mononucleosis. Clin Exp Immunol. 2008; 153: 231–9.
    OpenUrlCrossRefPubMed
  37. ↵
    2. Kim ST,
    3. Cristescu R,
    4. Bass AJ,
    5. Kim KM,
    6. Odegaard JI,
    7. Kim K, et al.
    Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nat Med. 2018; 24: 1449–58.
    OpenUrlCrossRefPubMed
  38. ↵
    2. Rouleau M,
    3. Patel A,
    4. Hendzel MJ,
    5. Kaufmann SH,
    6. Poirier GG.
    PARP inhibition: PARP1 and beyond. Nat Rev Cancer. 2010; 10: 293–301.
    OpenUrlCrossRefPubMedWeb of Science
  39. ↵
    2. Robson M,
    3. Im SA,
    4. Senkus E,
    5. Xu B,
    6. Domchek SM,
    7. Masuda N, et al.
    Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017; 377: 523–33.
    OpenUrlCrossRefPubMed
    2. Litton JK,
    3. Rugo HS,
    4. Ettl J,
    5. Hurvitz SA,
    6. Goncalves A,
    7. Lee KH, et al.
    Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018; 379: 753–63.
    OpenUrlCrossRefPubMed
  41. ↵
    2. Ledermann J,
    3. Harter P,
    4. Gourley C,
    5. Friedlander M,
    6. Vergote I,
    7. Rustin G, et al.
    Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012; 366: 1382–92.
    OpenUrlCrossRefPubMedWeb of Science
  42. ↵
    2. Caulfield SE,
    3. Davis CC,
    4. Byers KF.
    Olaparib: a novel therapy for metastatic breast cancer in patients with a BRCA1/2 mutation. J Adv Pract Oncol. 2019; 10: 167–74.
    OpenUrl
  43. ↵
    2. Norquist BM,
    3. Harrell MI,
    4. Brady MF,
    5. Walsh T,
    6. Lee MK,
    7. Gulsuner S, et al.
    Inherited mutations in women with ovarian carcinoma. JAMA Oncol. 2016; 2: 482–90.
    OpenUrl
  44. ↵
    2. Bang YJ,
    3. Xu RH,
    4. Chin K,
    5. Lee KW,
    6. Park SH,
    7. Rha SY, et al.
    Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017; 18: 1637–51.
    OpenUrlCrossRefPubMed
  45. ↵
    2. Le DT,
    3. Uram JN,
    4. Wang H,
    5. Bartlett BR,
    6. Kemberling H,
    7. Eyring AD, et al.
    PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015; 372: 2509–20.
    OpenUrlCrossRefPubMed
  46. ↵
    2. Tumeh PC,
    3. Harview CL,
    4. Yearley JH,
    5. Shintaku IP,
    6. Taylor EJM,
    7. Robert L, et al.
    PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014; 515: 568–71.
    OpenUrlCrossRefPubMedWeb of Science
  47. ↵
    2. Kluger HM,
    3. Zito CR,
    4. Barr ML,
    5. Baine MK,
    6. Chiang VL,
    7. Sznol M, et al.
    Characterization of PD-L1 expression and associated T-cell infiltrates in metastatic melanoma samples from variable anatomic sites. Clin Cancer Res. 2015; 21: 3052–60.
    OpenUrlAbstract/FREE Full Text
  48. ↵
    2. Geddert H,
    3. zur Hausen A,
    4. Gabbert HE,
    5. Sarbia M.
    EBV-infection in cardiac and non-cardiac gastric adenocarcinomas is associated with promoter methylation of p16, p14 and APC, but not hMLH1. Cell Oncol. 2011; 34: 209–14.
    OpenUrl
  49. ↵
    2. Li A,
    3. Yi M,
    4. Qin S,
    5. Chu Q,
    6. Luo S,
    7. Wu K.
    Prospects for combining immune checkpoint blockade with PARP inhibition. J Hematol Oncol. 2019; 12: 98.
    OpenUrlPubMed
Back to top

In this issue

Print
Download PDF
Email Article
Citation Tools

Jump to section

Subjects

Keywords