Sun Young Kim

Germline APC I1307K and MITF E318K variants in a patient with high-grade serous ovarian carcinoma: A case report

We report the case of a 76‑year‑old woman with high‑grade serous ovarian carcinoma (HGSOC) who was found to carry germline variants in APC I1307K and MITF E318K. Although neither variant is an established contributor to ovarian cancer risk, their co‑occurrence raises the possibility of polygenic or modifier effects on tumor susceptibility. The APC I1307K allele is a founder variant linked to increased colorectal cancer risk through the creation of a hypermutable region that predisposes to somatic mutations rather than classical tumor‑suppressor inactivation. In contrast, MITF E318K is a gain‑of‑function variant associated with melanoma and renal cell carcinoma, acting through altered transcriptional regulation that promotes cell proliferation and survival. While these genes do not interact directly, both converge on signaling pathways-WNT/β‑catenin, MAPK/ERK, and PI3K/AKT-that are widely implicated in ovarian carcinogenesis. There is a possibility that HGSOC in this patient is sporadic and unrelated to these two variants. Nevertheless, the case underscores the importance of comprehensive germline testing and highlights potential, yet underexplored, genetic interactions that may influence ovarian cancer risk. To our knowledge, this represents the first reported case of HGSOC in a patient harboring both variants, offering a hypothesis‑generating observation for future investigation.

Update on Cancer Screening in Children with Syndromes of Bone Lesions, Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome, and Other Rare Syndromes

Abstract The management of children with syndromes associated with an increased risk of benign and malignant neoplasms is a complex challenge for health care professionals. The 2023 American Association for Cancer Research Childhood Cancer Predisposition Workshop provided updated consensus guidelines on cancer surveillance in these syndromes, aiming to improve early detection and intervention and reduce morbidity associated with such neoplasms. In this article, we review several of the rare conditions discussed in this workshop. Ollier disease and Maffucci syndrome are enchondromatoses (disorders featuring benign bone lesions) with up to 50% risk of malignancy, including chondrosarcoma. These patients require surveillance with baseline whole-body MRI and routine monitoring of potential malignant transformation of bony lesions. Hereditary multiple osteochondromas carry a lower risk of chondrosarcoma (<6%) but still require lifelong surveillance and baseline imaging. Related syndromes of benign bone lesions are also described. Hereditary leiomyomatosis and renal cell carcinoma syndrome, associated with fumarate hydratase pathogenic variants, is discussed in detail. Surveillance for renal cell carcinoma in pediatric age is recommended, as well as prompt intervention when a lesion is detected. Schinzel–Giedion syndrome and Rubinstein–Taybi syndrome are described for their associated malignancies and other complications, as well as expert consensus on the need for childhood cancer surveillance. Clinical recommendations, including imaging modalities and frequency of screenings, are proposed and are tailored to each syndrome's age-specific tumor risk profile. In all syndromes, patients and their families should be educated about the potential malignancy risk and advised to seek medical care for rapid growth of a mass, persistent pain, or other unexplained symptoms.