Illustrating the "Quiet Genome" Concept of SMARCA4 -Deficient Uterine Sarcoma Via Whole-Exome Sequencing: A Highly Aggressive Case in a Young Woman.
Hiroshi Yoshida, Kouya Shiraishi, Taro Yamanaka et al.
✦ AI-curated · Sources linked
Case in brief
A 23-year-old woman presented with a uterine mass larger than 15 cm. Histology showed undifferentiated epithelioid cells with rhabdoid features and focal phyllodes-like architecture, without a carcinomatous component. Tumor cells lacked SMARCA4 and SMARCA2 but retained SMARCB1; whole-exome sequencing identified biallelic SMARCA4 inactivation, microsatellite stability, low tumor mutational burden, and no additional canonical driver mutations. The findings supported SMARCA4-deficient undifferentiated uterine sarcoma. Despite hysterectomy and bilateral salpingo-oophorectomy, the disease rapidly disseminated and was refractory to gemcitabine/docetaxel; the patient died 6 months after surgery.
What made this case unusual
Whole-exome analysis corroborated a “quiet genome” in this aggressive sarcoma: biallelic SMARCA4 inactivation was found without additional canonical driver mutations or a TP53 mutation, despite hemizygous 17p loss.
Diagnostic / clinical pearl
When an undifferentiated uterine tumor overlaps morphologically with carcinoma, the combination of morphology, SWI/SNF-protein immunohistochemistry, and genomic profiling can support distinction of SMARCA4-deficient sarcoma from undifferentiated endometrial carcinoma.
Why it matters
The case adds exome-wide support for the quiet-genome concept in SMARCA4-deficient uterine sarcoma and highlights its genomic distinction from undifferentiated endometrial carcinoma.