Exploration of Targeted Anti-tumor Therapy

Table 3. Molecular alterations in ARID1A⁺ tumors

Tissue used for analysis	Molecular alterations in ARID1A	Hystology
Primary disease (diagnosis)	ARID1A-PTAR1 truncation, S2249*	Ovarian (clear cell)
	L1731fs4; Q372fs19	Endometrial (endometrioid)
	N104fs*7	Cervical
	P1175fs5; Q766fs67	Endometrial (endometrioid)
	Q372fs*19	Ovarian (clear cell)
	R727fs*84	Ovarian (clear cell)
	W2049*	Colorectal
	P224fs*8	Gastric
	Y2254*	Cervical (clear cell)
	S1171fs*22	Duodenal
	ARID1A truncation	Lung
	P146fs*86	Pancreas
	K1072fs*21-subclonal	Endometrial (endometrioid)
Relapsed disease	Q1409; S1609fs38	Endometrial (endometrioid)
	Q1519fs8; G623fs6	Endometrial (endometrioid)
	Q372fs*19	Endometrial
	Q567*	Ovarian (clear cell)
	W1073fs*32	Breast
	Y447*	Cervical
	Y788*	Ovarian (high grade)
	F2141fs59, M1564fs1	Endometrial (endometrioid)
Blood	ARID1A-ARHGEF40 truncation	Hepatocellular
	Q1327fs*11	Colorectal
	Q1579*	Breast
	Q754*	Lung

Return to article view

PTAR1: prenyltransferase alpha subunit repeat containing 1; ARHGEF40: Rho guanine nucleotide exchange factors gene 40

Declarations

Author contributions

RF: Conceptualization, Formal analysis, Data curation, Writing—review & editing. GD: Conceptualization, Supervision. MF and PL: Data curation. VA and FPS: Formal analysis. GS: Supervision. All authors read and approved the submitted version.

Conflicts of interest

RF, MF, PL, VA, and FPS declare that they have no conflicts of interest. GS has served on advisory boards for TESARO Bio Italy S.r.l, Johnson & Johnson, Clovis Oncology Italy S.r.l. He received support for travel or accommodation from MSD Italy S.r.l and Clovis Oncology Italy S.r.l. GD has served on advisory board of Beigene and received support for travel and accommodation from Roche.

Ethical approval

The study complies with the declaration of Helsinki and was approved by the Ethics Committee of Fondazione Policlinico Universitario A. Gemelli IRCCS (ID5261).

Consent to participate

Informed consent to participate in the study was obtained from all participants.

Consent to publication

Not applicable.

Availability of data and materials

The data generated in the present study can be requested from the corresponding author (Gennaro Daniele, gennaro.daniele@policlinicogemelli.it).

Funding

Not applicable.

Copyright

References

Mathur R. ARID1A loss in cancer: towards a mechanistic understanding. Pharmacol Ther. 2018;190:15–23. [DOI] [PubMed]

Bosse T, ter Haar NT, Seeber LM, v Diest PJ, Hes FJ, Vasen HF, et al. Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations, TP53 and microsatellite instability in endometrial cancer. Mod Pathol. 2013;26:1525–35. [DOI] [PubMed]

Inoue H, Furukawa T, Giannakopoulos S, Zhou S, King DS, Tanese N. Largest subunits of the human SWI/SNF chromatin-remodeling complex promote transcriptional activation by steroid hormone receptors. J Biol Chem. 2002;277:41674–85. [DOI] [PubMed]

Wilsker D, Patsialou A, Zumbrun SD, Kim S, Chen Y, Dallas PB, et al. The DNA-binding properties of the ARID-containing subunits of yeast and mammalian SWI/SNF complexes. Nucleic Acids Res. 2004;32:1345–53. [DOI] [PubMed] [PMC]

Mandal J, Mandal P, Wang TL, Shih IM. Treating ARID1A mutated cancers by harnessing synthetic lethality and DNA damage response. J Biomed Sci. 2022;29:71. [DOI] [PubMed] [PMC]

Jones S, Wang TL, Shih IeM, Mao TL, Nakayama K, Roden R, et al. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science. 2010;330:228–31. [DOI] [PubMed] [PMC]

Luo Q, Wu X, Chang W, Zhao P, Zhu X, Chen H, et al. ARID1A hypermethylation disrupts transcriptional homeostasis to promote squamous cell carcinoma progression. Cancer Res. 2020;80:406–17. Erratum in: Cancer Res. 2020;80:4302. [DOI] [PubMed]

Mullen J, Kato S, Sicklick JK, Kurzrock R. Targeting ARID1A mutations in cancer. Cancer Treat Rev. 2021;100:102287. [DOI] [PubMed]

Jiang T, Chen X, Su C, Ren S, Zhou C. Pan-cancer analysis of ARID1A alterations as biomarkers for immunotherapy outcomes. J Cancer. 2020;11:776–80. [DOI] [PubMed] [PMC]

10.

Khosrowjerdi SJ, Horick NK, Clark JW, Parikh AR, Allen JN, Nipp RD, et al. Clinical and mutational profile of ARID1A-mutated gastrointestinal cancers: duration of response to platinum-based chemotherapy. J Clin Oncol. 2021;39:e15611. [DOI]

11.

Kato MK, Yoshida H, Tanase Y, Uno M, Ishikawa M, Kato T. Loss of ARID1A expression as a favorable prognostic factor in early-stage grade 3 endometrioid endometrial carcinoma patients. Pathol Oncol Res. 2021;27:598550. [DOI] [PubMed] [PMC]

12.

Wang X, Che K, Shi T, Liu Q, Xu X, Wu H, et al. Loss of ARID1A expression is associated with systemic inflammation markers and has important prognostic significance in gastric cancer. J Cancer Res Clin Oncol. 2022;148:1583–95. [DOI] [PubMed]

13.

Luchini C, Veronese N, Solmi M, Cho H, Kim JH, Chou A, et al. Prognostic role and implications of mutation status of tumor suppressor gene ARID1A in cancer: a systematic review and meta-analysis. Oncotarget. 2015;6:39088–97. [DOI] [PubMed] [PMC]

14.

Okamura R, Kato S, Lee S, Jimenez RE, Sicklick JK, Kurzrock R. ARID1A alterations function as a biomarker for longer progression-free survival after anti-PD-1/PD-L1 immunotherapy. J Immunother Cancer. 2020;8:e000438. [DOI] [PubMed] [PMC]

15.

Wang N, Qin Y, Du F, Wang X, Song C. Prevalence of SWI/SNF genomic alterations in cancer and association with the response to immune checkpoint inhibitors: a systematic review and meta-analysis. Gene. 2022;834:146638. [DOI] [PubMed]

16.

Daniel Ampanattu S, Ahmed G, Thapa B, Janardan A, Vallejos A, Taylor B, et al. Predictive impact of ARID1A status in solid tumors. Eur J Cancer. 2022;174:S96. [DOI]

17.

Shen J, Peng Y, Wei L, Zhang W, Yang L, Lan L, et al. ARID1A deficiency impairs the DNA damage checkpoint and sensitizes cells to PARP inhibitors. Cancer Discov. 2015;5:752–67. [DOI] [PubMed] [PMC]

18.

Williamson CT, Miller R, Pemberton HN, Jones SE, Campbell J, Konde A, et al. ATR inhibitors as a synthetic lethal therapy for tumours deficient in ARID1A. Nat Commun. 2016;7:13837. [DOI] [PubMed] [PMC]

19.

Frampton GM, Fichtenholtz A, Otto GA, Wang K, Downing SR, He J, et al. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol. 2013;31:1023–31. [DOI] [PubMed] [PMC]

20.

ClinicalTrials.gov [Internet]. [cited 2023 Feb 2]. Available from: https://clinicaltrials.gov

21.

Banerjee S, Stewart J, Porta N, Toms C, Leary A, Lheureux S, et al. ATARI trial: ATR inhibitor in combination with olaparib in gynecological cancers with ARID1A loss or no loss (ENGOT/GYN1/NCRI). Int J Gynecol Cancer. 2021;31:1471–5. [DOI] [PubMed] [PMC]

22.

Guan B, Rahmanto YS, Wu RC, Wang Y, Wang Z, Wang TL, et al. Roles of deletion of Arid1a, a tumor suppressor, in mouse ovarian tumorigenesis. J Natl Cancer Inst. 2014;106:dju146. [DOI] [PubMed] [PMC]

23.

Samartzis EP, Gutsche K, Dedes KJ, Fink D, Stucki M, Imesch P. Loss of ARID1A expression sensitizes cancer cells to PI3K- and AKT-inhibition. Oncotarget. 2014;5:5295–303. [DOI] [PubMed] [PMC]

24.

Kurzrock R, Aggarwal C, Weipert C, Kiedrowski L, Riess J, Lenz HJ, et al. Prevalence of ARID1A mutations in cell-free circulating tumor DNA in a cohort of 71,301 patients and association with driver co-alterations. Cancers (Basel). 2022;14:4281. [DOI] [PubMed] [PMC]

25.

Chaluts D, Dullea JT, Ali M, Vasan V, Devarajan A, Rutland JW, et al. ARID1A mutation associated with recurrence and shorter progression-free survival in atypical meningiomas. J Cancer Res Clin Oncol. 2023;149:5165–72. [DOI] [PubMed]