{"doi":"10.1158/1078-0432.c.6532713.v1","title":"Data from Clinico-genomic Characterization of <i>ATM</i> and HRD in Pancreas Cancer: Application for Practice","abstract":"<div>AbstractPurpose:<p>Characterizing germline and somatic <i>ATM</i> variants (g<i>ATM</i>m, s<i>ATM</i>m) zygosity and their contribution to homologous recombination deficiency (HRD) is important for therapeutic strategy in pancreatic ductal adenocarcinoma (PDAC).</p>Experimental Design:<p>Clinico-genomic data for patients with PDAC and other cancers with <i>ATM</i> variants were abstracted. Genomic instability scores (GIS) were derived from <i>ATM</i>-mutant cancers and overall survival (OS) was evaluated.</p>Results:<p>Forty-six patients had PDAC and pathogenic <i>ATM</i> variants including 24 (52%) stage III/IV: g<i>ATM</i>m (<i>N</i> = 24), and s<i>ATM</i>m (<i>N</i> = 22). Twenty-seven (59%) had biallelic, 15 (33%) monoallelic, and 4 indeterminate (8%) variants. Median OS for advanced-stage cohort at diagnosis (<i>N</i> = 24) was 19.7 months [95% confidence interval (CI): 12.3–not reached (NR)], 27.1 months (95% CI: 22.7–NR) for g<i>ATM</i>m (<i>n</i> = 11), and 12.3 months for s<i>ATM</i>m (<i>n</i> = 13; 95% CI: 11.9–NR; <i>P</i> = 0.025). GIS was computed for 33 patients with PDAC and compared with other <i>ATM</i>-mutant cancers enriched for HRD. The median was lower (median, 11; range, 2–29) relative to breast (<a href=\"#bib18 bib3 bib4 bib5 bib6 bib7 bib8 bib9 bib10 bib11 bib12 bib13 bib14 bib15 bib16 bib17 bib18 bib19 bib20 bib21 bib22 bib23 bib24 bib25 bib26 bib27 bib28 bib29 bib30 bib31 bib32 bib33 bib34 bib35 bib36 bib37 bib38 bib39 bib40 bib41 bib42 bib43 bib44 bib45 bib46 bib47 bib48 bib49 bib50 bib51 bib52 bib53 bib54 bib55\" target=\"_blank\">18, 3–55</a>) or ovarian (<a href=\"#bib25 bib3 bib4 bib5 bib6 bib7 bib8 bib9 bib10 bib11 bib12 bib13 bib14 bib15 bib16 bib17 bib18 bib19 bib20 bib21 bib22 bib23 bib24 bib25 bib26 bib27 bib28 bib29 bib30 bib31 bib32 bib33 bib34 bib35 bib36 bib37 bib38 bib39 bib40 bib41 bib42 bib43 bib44 bib45 bib46 bib47 bib48 bib49 bib50 bib51 bib52 bib53 bib54 bib55 bib56\" target=\"_blank\">25, 3–56</a>) <i>ATM</i>-mutant cancers (<i>P</i> < 0.001 and <i>P</i> = 0.003, respectively). Interestingly, biallelic pathogenic <i>ATM</i> variants were mutually exclusive with <i>TP53</i>. Other canonical driver gene (<i>KRAS, CDKN2A, SMAD4</i>) variants were less frequent in <i>ATM</i>-mutant PDAC.</p>Conclusions:<p><i>ATM</i> variants in PDAC represent a distinct biologic group and appear to have favorable OS. Nonetheless, pathogenic <i>ATM</i> variants do not confer an HRD signature in PDAC and <i>ATM</i> should be considered as a non-core HR gene in this disease.</p></div>","journal":null,"year":2023,"id":405601,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":0.0,"corpus_rank":10331,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.9104,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":683055,"name":"Catherine O’Connor","orcid":"0000-0003-4080-9149","position":1,"is_corresponding":false},{"id":271416,"name":"Chaitanya Bandlamudi","orcid":"0000-0003-1108-4919","position":2,"is_corresponding":false},{"id":874395,"name":"Daniella Forman","orcid":null,"position":3,"is_corresponding":false},{"id":231583,"name":"Joanne F. Chou","orcid":"0000-0002-6866-2022","position":4,"is_corresponding":false},{"id":873707,"name":"Shigeaki Umeda","orcid":"0000-0001-5693-1515","position":5,"is_corresponding":false},{"id":377112,"name":"Marsha Reyngold","orcid":"0000-0001-9475-146X","position":6,"is_corresponding":false},{"id":90751,"name":"Anna M. Varghese","orcid":"0000-0001-5426-0885","position":7,"is_corresponding":false},{"id":873708,"name":"Fergus Keane","orcid":"0000-0001-6651-2090","position":8,"is_corresponding":false},{"id":873709,"name":"Fiyinfolu Balogun","orcid":"0000-0003-4703-1560","position":9,"is_corresponding":false},{"id":242188,"name":"Kenneth H. Yu","orcid":"0000-0002-4774-2672","position":10,"is_corresponding":false},{"id":231591,"name":"David P. Kelsen","orcid":"0000-0001-6139-438X","position":11,"is_corresponding":false},{"id":305046,"name":"Christopher H. Crane","orcid":"0000-0001-5143-2784","position":12,"is_corresponding":false},{"id":231596,"name":"Marinela Capanu","orcid":"0000-0003-4953-3193","position":13,"is_corresponding":false},{"id":14372,"name":"Christine A. Iacobuzio–Donahue","orcid":"0000-0002-4672-3023","position":14,"is_corresponding":false},{"id":242198,"name":"Eileen M. O’Reilly","orcid":"0000-0002-8076-9199","position":15,"is_corresponding":false},{"id":242186,"name":"Wungki Park","orcid":"0000-0002-8006-3102","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:20:54.430249Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}