Biomedical subjects

Pier Selenica

Publications and source records attributed to Pier Selenica.

3 recordsLinked to original sources

PubMed2026

The Genomic Landscape of MYC-, MYCL-, and MYCN-Amplified Solid Tumors.

PURPOSE: MYC, MYCN, and MYCL amplifications are recurrent oncogenic events across solid tumors. Currently, no standardized selection biomarker is available to identify patients with MYC-dependent tumors. EXPERIMENTAL DESIGN: We analyzed copy-number alterations of MYC family genes and their features in more than 68,000 tumor-normal paired samples from pediatric and adult patients sequenced with MSK-IMPACT (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) and annotated with FACETS (Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing). The relationship between amplification features and MYC mRNA expression levels were evaluated in more than 10,000 samples from The Cancer Genome Atlas (TCGA). RESULTS: Across MSK Cancer Center samples, MYC amplifications were most common, found in 2,949 samples compared with 310 in MYCL and 217 in MYCN. Although MYCN and MYCL amplifications were predominantly focal (<10 Mb, 79% and 93%, respectively), MYC amplifications were frequently broader (>10 Mb, 62%). Although most tumor types showed similar features between broad and focal amplifications of MYC, in select cancer types, we identified differing co-occurrence and mutual exclusivity patterns with other disease-specific drivers. Furthermore, although MYC-amplified TCGA samples showed higher mRNA expression than wild-type ones, the focality of MYC amplification was seen to have limited influence on expression levels. CONCLUSIONS: Our results suggest that MYC dependency likely depends on many factors, including, but not limited to, total copy number of the detected amplification, lineage-specific factors, concomitant presence or absence of additional oncogenic alterations, and in some cases amplification focality.

Humans↗

PubMed2026

Landscape of genetic alterations affecting cancer genes in primary and advanced malignant phyllodes tumours.

BACKGROUND: Malignant phyllodes tumours (MPT) are aggressive breast fibroepithelial neoplasms. Their rarity has limited their genetic characterization, and associations with genetic ancestry and progression drivers remain poorly understood. Prior studies suggest two evolutionary pathways according to MED12 mutational status. We sought to determine the repertoire of somatic genetic alterations in cancer genes in primary versus metastatic/recurrent MPTs, and according to MED12 mutational status and genetic ancestry. MATERIALS AND METHODS: We analysed the paired tumour-normal targeting sequencing data (up to 505 cancer-related genes) of 31 MPTs (primary, n = 20; metastatic/recurrent, n = 11). RESULTS: Metastatic/recurrent MPTs harboured a numerically higher frequency of genetic alterations in CDKN2A/2B (55% vs. 25%). Moreover, analysis of an MPT case with paired primary and metastatic samples revealed a CDKN2A/2B homozygous deletion restricted to the metastatic sample, suggesting a role for CDKN2A/2B in progression. Compared with MED12-wild type MPTs, MED12-mutant MPTs had higher tumour mutation burden (P = 0.002), frequency of TERT promoter (82% vs. 35%; P = 0.02) and RB1 mutations (45% vs. 5%; P = 0.01). Genetic alterations in the PI3K pathway, including PIK3CA and PTEN, were only present in MED12-wild type MPTs, and absent in MED12-mutant cases (15% vs. 0%; P > 0.05). Furthermore, genetic alterations in EGFR were restricted to MPTs from patients of European genetic ancestry and absent in those of Asian ancestry (43% vs. 0%; P > 0.05). CONCLUSIONS: Taken together, the repertoire of genetic alterations in primary and metastatic/recurrent MPTs shows overlap, and CDKN2A/2B homozygous deletions may play a role in progression. Additionally, molecular profiles of MPTs may vary according to genetic ancestry and MED12 mutational status.

Humans↗

PubMed2025

A Subset of Serous Tubal Intraepithelial Carcinoma (STIC)-Like Lesions and Concurrent High-Grade Endometrial Carcinoma Are Genomically Related Entities.

In patients with high-grade endometrial carcinoma (HG-EC), concurrent isolated serous tubal intraepithelial carcinoma (STIC) or STIC-like lesions (STIC-LLs) in the fallopian tube(s) may be found. We sought to determine whether concurrently diagnosed HG-ECs and STIC-LLs are genetically related. Six HG-ECs, including serous carcinomas (n = 4) and carcinosarcomas with serous epithelial component (n = 2), with cooccurring STIC-LLs were identified and subjected to microdissection, DNA extraction, and panel sequencing targeting 468 cancer-related genes or, if DNA quantities were limited, to Sanger sequencing. WT1 and p53 protein expression was assessed by immunohistochemistry. We found that 3 HG-ECs and concurrent STIC-LLs shared pathogenic mutations, such as TP53 hotspot, NF2, FBXW7, and PIK3CA mutations. Immunohistochemical analysis revealed that the HG-EC of case 5 lacked WT1 expression and had aberrant p53 expression, although the matched STIC-LL displayed diffuse WT1 expression. Of the remaining 3 cases that did not show evidence of genetic relatedness based on the targeted sequencing panel, 1 STIC-LL harbored a clonal TP53 missense mutation, whereas the matched HG-EC had a distinct clonal TP53 hotspot mutation, a clonal FBXW7 hotspot mutation, and ERBB2 amplification. At the protein level, the p53 expression patterns of the HG-ECs and STIC-LLs were concordant in these 3 cases. Here, we demonstrate that cooccurring HG-ECs and STIC-LLs are genetically related in a subset of cases.

Humans↗