Genes Chromosomes and Cancer

doi: 10.1002/gcc.23167pmid: N/A

Takahashi, Kotaro; Yachida, Nozomi; Tamura, Ryo; Adachi, Sosuke; Kondo, Shuhei; Abé, Tatsuya; Umezu, Hajime; Nyuzuki, Hiromi; Okuda, Shujiro; Nakaoka, Hirofumi; Yoshihara, Kosuke

doi: 10.1002/gcc.23231pmid: 38459936

Lynch syndrome‐associated endometrial cancer patients often present multiple synchronous tumors and this assessment can affect treatment strategies. We present a case of a 27‐year‐old woman with tumors in the uterine corpus, cervix, and ovaries who was diagnosed with endometrial cancer and exhibited cervical invasion and ovarian metastasis. Her family history suggested Lynch syndrome, and genetic testing identified a variant of uncertain significance, MLH1 p.L582H. We conducted immunohistochemical staining, microsatellite instability analysis, and Sanger sequencing for Lynch syndrome‐associated cancers in three generations of the family and identified consistent MLH1 loss. Whole‐exome sequencing for the corpus, cervical, and ovarian tumors of the proband identified a copy‐neutral loss of heterozygosity (LOH) occurring at the MLH1 position in all tumors. This indicated that the germline variant and the copy‐neutral LOH led to biallelic loss of MLH1 and was the cause of cancer initiation. All tumors shared a portion of somatic mutations with high mutant allele frequencies, suggesting a common clonal origin. There were no mutations shared only between the cervix and ovary samples. The profiles of mutant allele frequencies shared between the corpus and cervix or ovary indicated that two different subclones originating from the corpus independently metastasized to the cervix or ovary. Additionally, all tumors presented unique mutations in endometrial cancer‐associated genes such as ARID1A and PIK3CA. In conclusion, we demonstrated clonal origin and genomic diversity in a Lynch syndrome‐associated endometrial cancer, suggesting the importance of evaluating multiple sites in Lynch syndrome patients with synchronous tumors.

Yeung, Maximus C. F.; Dermawan, Josephine K.; Liu, Anthony P. Y.; Lam, Albert Y. L.; Antonescu, Cristina R.; Shek, Tony W. H.

doi: 10.1002/gcc.23227pmid: 38517106

Furtado, Larissa V.; Cardenas, Maria; Santiago, Teresa; Ruiz, Robert E.; Shi, Zonggao; Pappo, Alberto; Kacar, Marija

doi: 10.1002/gcc.23230pmid: 38459940

Childhood melanoma is a rare and biologically heterogeneous pediatric malignancy. The differential diagnosis of pediatric melanoma is usually broad, including a wide variety of spindle cell or epithelioid neoplasms. Different molecular alterations affecting the MAPK and PI3K/AKT/mTOR pathways, tumor suppressor genes, and telomerase reactivation have been implicated in melanoma tumorigenesis and progression. Here, we report a novel MED15::ATF1 fusion in a pediatric melanoma with spitzoid features and an aggressive clinical course.

Fontanges, Quitterie; Dubos, Paul; Lesluyes, Tom; Laizet, Yec'han; Velasco, Valérie; Meléndez, Bárbara; D'Haene, Nicky; Oliva, Esther; Young, Robert H.; Mayeur, Laetitia; Rebier, Flora; Alamé, Mélissa; Larmonier, Claire; Devouassoux‐Shisheboran, Mojgan;