{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:42:20Z","timestamp":1790764940905,"version":"4.1.0"},"reference-count":40,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"24","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2003,12,15]]},"abstract":"<jats:p> Purpose: Despite recognition that second malignant neoplasms (SMNs) contribute significantly to mortality after the successful treatment of Hodgkin\u2019s disease (HD), little is known about the molecular events leading to secondary tumors. Factors contributing to second cancer risk include the carcinogenic effects of ionizing radiation and chemotherapy, in combination with possible host susceptibility. To clarify whether host genetic factors contribute to secondary tumorigenesis, we performed mutational analyses of the TP53, BRCA1, and BRCA2 tumor suppressor genes in a cohort of 44 HD patients developing one or more SMN. <\/jats:p><jats:p> Patients and Methods: Family cancer histories and constitutional DNA samples were obtained from 44 HD patients with SMNs identified. Using DNA-based sequencing, we evaluated the TP53 gene in all 44 patients. Nineteen female patients developing one or more secondary breast cancer were also analyzed for mutations in the BRCA1 and BRCA2 breast cancer\u2013susceptibility genes. <\/jats:p><jats:p> Results: Nineteen patients (43%) had more than one SMN, and 12 patients (27%) had a positive family history of cancer. One of 44 patients tested for TP53 harbored a novel homozygous germline abnormality. One of 19 patients tested for BRCA2 carried a previously described heterozygous inactivating mutation. We identified no germline BRCA1 mutations. <\/jats:p><jats:p> Conclusion: Despite features suggestive of genetic predisposition, the TP53, BRCA1, and BRCA2 genes were not frequently mutated in this cohort of HD patients developing SMNs. Larger studies of these genes or investigations of other genes involved in cellular DNA damage response pathways may identify host genetic factors that contribute to secondary tumorigenesis. <\/jats:p>","DOI":"10.1200\/jco.2003.12.042","type":"journal-article","created":{"date-parts":[[2003,12,12]],"date-time":"2003-12-12T22:02:59Z","timestamp":1071266579000},"page":"4505-4509","source":"Crossref","is-referenced-by-count":30,"title":["<i>TP53, BRCA1<\/i>, and <i>BRCA2<\/i> Tumor Suppressor Genes Are Not Commonly Mutated in Survivors of Hodgkin\u2019s Disease With Second Primary Neoplasms"],"prefix":"10.1200","volume":"21","author":[{"given":"Kim E.","family":"Nichols","sequence":"first","affiliation":[{"name":"From the Departments of Pediatric Oncology and Human Genetics, Children\u2019s Hospital of Philadelphia; Department of Genetics, University of Pennsylvania, Philadelphia, PA; Departments of Pediatric Oncology and Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA; Department of Pediatric Hematology\/Oncology, Children\u2019s Hospital and Medical Center, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Heath","sequence":"additional","affiliation":[{"name":"From the Departments of Pediatric Oncology and Human Genetics, Children\u2019s Hospital of Philadelphia; Department of Genetics, University of Pennsylvania, Philadelphia, PA; Departments of Pediatric Oncology and Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA; Department of Pediatric Hematology\/Oncology, Children\u2019s Hospital and Medical Center, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra","family":"Friedman","sequence":"additional","affiliation":[{"name":"From the Departments of Pediatric Oncology and Human Genetics, Children\u2019s Hospital of Philadelphia; Department of Genetics, University of Pennsylvania, Philadelphia, PA; Departments of Pediatric Oncology and Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA; Department of Pediatric Hematology\/Oncology, Children\u2019s Hospital and Medical Center, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaclyn A.","family":"Biegel","sequence":"additional","affiliation":[{"name":"From the Departments of Pediatric Oncology and Human Genetics, Children\u2019s Hospital of Philadelphia; Department of Genetics, University of Pennsylvania, Philadelphia, PA; Departments of Pediatric Oncology and Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA; Department of Pediatric Hematology\/Oncology, Children\u2019s Hospital and Medical Center, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arupa","family":"Ganguly","sequence":"additional","affiliation":[{"name":"From the Departments of Pediatric Oncology and Human Genetics, Children\u2019s Hospital of Philadelphia; Department of Genetics, University of Pennsylvania, Philadelphia, PA; Departments of Pediatric Oncology and Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA; Department of Pediatric Hematology\/Oncology, Children\u2019s Hospital and Medical Center, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Mauch","sequence":"additional","affiliation":[{"name":"From the Departments of Pediatric Oncology and Human Genetics, Children\u2019s Hospital of Philadelphia; Department of Genetics, University of Pennsylvania, Philadelphia, PA; Departments of Pediatric Oncology and Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA; Department of Pediatric Hematology\/Oncology, Children\u2019s Hospital and Medical Center, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Diller","sequence":"additional","affiliation":[{"name":"From the Departments of Pediatric Oncology and Human Genetics, Children\u2019s Hospital of Philadelphia; Department of Genetics, University of Pennsylvania, Philadelphia, PA; Departments of Pediatric Oncology and Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA; Department of Pediatric Hematology\/Oncology, Children\u2019s Hospital and Medical Center, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V83.2.318.318"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.9.3625.bloodjournal8793625"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1995.13.8.2016"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-02-0634"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.09.038"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199603213341201"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199603213341210"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1998.16.2.536"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1016\/S0720-048X(00)00291-6"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2001.19.2.464"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1999.17.4.1259"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1086\/302746"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-71-4-747"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.10.11.5772"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/90.8.606"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199205143262002"},{"key":"R17","unstructured":"Nichols KE, Malkin D, Garber JE, et al: Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. 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