Your browser doesn't support javascript.
loading
The Impact of Germline Alterations in Appendiceal Adenocarcinoma.
Foote, Michael B; Walch, Henry; Kemel, Yelena; Vakiani, Efsevia; Johannet, Paul; Sheehan, Margaret; Chatila, Walid; Chung, Sebastian; Nash, Garrett M; Maio, Anna; Shia, Jinru; Mandelker, Diana; Berger, Michael; Schultz, Nikolaus; Diaz, Luis A; Cercek, Andrea; Stadler, Zsofia K.
Afiliação
  • Foote MB; Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Walch H; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Kemel Y; Niehaus Center for Inherited Cancer Genomics, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Vakiani E; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Johannet P; Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Sheehan M; Niehaus Center for Inherited Cancer Genomics, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Chatila W; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Chung S; Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Nash GM; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Maio A; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Shia J; Niehaus Center for Inherited Cancer Genomics, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Mandelker D; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Berger M; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Schultz N; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Diaz LA; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Cercek A; Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Stadler ZK; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Clin Cancer Res ; 29(14): 2631-2637, 2023 07 14.
Article em En | MEDLINE | ID: mdl-37289003
ABSTRACT

PURPOSE:

More than 10% of assessed patients with appendiceal adenocarcinoma have a pathogenic (P) or likely pathogenic (LP) germline variant, including genes implicated in heritable gastrointestinal cancer syndromes, such as Lynch syndrome. We defined the clinical and molecular impact of heritable alterations in appendiceal adenocarcinoma to evaluate the need for dedicated appendiceal screening and prevention strategies in patients with LP/P germline variants. EXPERIMENTAL

DESIGN:

We performed an integrated germline and somatic molecular analysis for patients with confirmed appendiceal adenocarcinoma. Patients underwent paired tumor-normal sequencing for up to 90 hereditary cancer risk genes and 505 genes for somatic mutation profiling. We defined the cooccurrence of LP/P germline variants and second-hit pathogenic somatic alterations. The associations between germline variants and patient clinicopathologic features were also evaluated.

RESULTS:

Twenty-five of 237 patients (10.5%) carried pathogenic or likely pathogenic germline variants in cancer susceptibility genes. Clinicopathologic characteristics and appendiceal adenocarcinoma-specific survival were similar in patients with or without germline variants. Most (92%, N = 23/25) patients with germline variants demonstrated no second-hit somatic alterations, including loss of heterozygosity. Two patients with a germline APC I1307K low-penetrance founder variant exhibited secondary somatic pathogenic alterations in APC. However, only one patient tumor exhibited APC-mediated WNT signaling dysregulation a plausible consequence of multiple somatic APC mutations with no germline variant contribution. Four patients had germline variants in PMS2 or MSH2 associated with Lynch syndrome, yet their cancers were microsatellite-stable.

CONCLUSIONS:

Germline variants are likely incidental without a contributory driver role in appendiceal adenocarcinoma. Appendiceal adenocarcinoma screening in patients with germline variants is not clearly merited.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias do Apêndice / Síndromes Neoplásicas Hereditárias / Adenocarcinoma / Neoplasias Colorretais Hereditárias sem Polipose Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias do Apêndice / Síndromes Neoplásicas Hereditárias / Adenocarcinoma / Neoplasias Colorretais Hereditárias sem Polipose Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article