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Pathogenic\n                      <jats:italic>STK11<\/jats:italic>\n                      variants explain only a minority of reported cases, suggesting additional susceptibility genes. However, the genetic landscape of SMMN\u2010FGT remains poorly characterised.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Whole\u2010exome sequencing was performed on 19 lesions and matched normal tissues from 13 cases with SMMN\u2010FGT. Pathogenic germline variants in cancer\u2010predisposition genes were identified, and their carrier frequencies were compared with those in common gynaecologic cancers. The somatic mutational landscape of SMMN\u2010FGT was characterised and compared with conventional cervical cancers. Clonal analyses were performed to identify candidate driver genes, and the functional effects of\n                      <jats:italic>KDM5C<\/jats:italic>\n                      were evaluated in vitro using siRNA\u2010mediated knockdown and plasmid\u2010mediated overexpression assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Germline analysis showed a markedly higher prevalence of pathogenic variants in cancer\u2010associated genes in SMMN\u2010FGT (38.5%) than common gynaecologic cancers (4.4%\u20138.6%). Two cases carried pathogenic\n                      <jats:italic>BRCA1<\/jats:italic>\n                      variants, raising the possibility that SMMN\u2010FGT may be part of a broader\n                      <jats:italic>BRCA1<\/jats:italic>\n                      \u2010associated phenotypic spectrum. Somatic profiling identified\n                      <jats:italic>TP53<\/jats:italic>\n                      mutations in five (26.3%) of 19 total lesions, four (80.0%) of which were malignant. Gastric\u2010type cervical adenocarcinoma (GCA) was the most common malignant subtype of SMMN\u2010FGT, with\n                      <jats:italic>TP53<\/jats:italic>\n                      mutations detected in three (42.9%) of seven GCA lesions and no\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      mutations. By contrast, conventional cervical cancers frequently harbour\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      mutations (27%\u201341%), whereas\n                      <jats:italic>TP53<\/jats:italic>\n                      mutations are relatively uncommon. Clonal analysis identified\n                      <jats:italic>KDM5C<\/jats:italic>\n                      as a candidate driver.\n                      <jats:italic>KDM5C<\/jats:italic>\n                      overexpression reduced cell viability, migration and invasion and increased apoptosis, whereas its knockdown produced the opposite effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      SMMN\u2010FGT has a distinct genetic profile characterised by an enrichment of pathogenic germline variants, and recurrent\n                      <jats:italic>TP53<\/jats:italic>\n                      mutations predominantly affecting malignant lesions.\n                      <jats:italic>KDM5C<\/jats:italic>\n                      may function as a candidate tumour suppressor. These findings advance our understanding of SMMN\u2010FGT pathogenesis and warrant further investigation of its diagnostic and therapeutic implications.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>Key Points<\/jats:title>\n                      <jats:p>\n                        <jats:list list-type=\"bullet\">\n                          <jats:list-item>\n                            <jats:p>SMMN\u2010FGT exhibits a distinct landscape of germline cancer\u2010predisposition variants.<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>\n                              <jats:italic>TP53<\/jats:italic>\n                              mutations are associated with malignant progression in SMMN\u2010FGT.\n                            <\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>\n                              <jats:italic>KDM5C<\/jats:italic>\n                              is identified as a potential tumour suppressor in SMMN\u2010FGT.\n                            <\/jats:p>\n                          <\/jats:list-item>\n                        <\/jats:list>\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70768","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T07:32:00Z","timestamp":1786951920000},"source":"Crossref","is-referenced-by-count":0,"title":["Germline predisposition and somatic mutational landscape in synchronous mucinous metaplasia and neoplasia of the female genital tract"],"prefix":"10.1002","volume":"16","author":[{"given":"Ying","family":"Yuan","sequence":"first","affiliation":[{"name":"Obstetrics and Gynecology Hospital, State Key Laboratory of Genetics and Development of Complex Phenotypes, Human Phenome Institute Fudan 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