bims-tumhet 2026-06-14 papers

bims-tumhet

Biomed News

on Tumor heterogeneity

Issue of 2026–06–14
seven papers selected by
Sergio Marchini, Humanitas Research

ESGO Statements on Opportunistic Salpingectomy for Prevention of Tubo-Ovarian Carcinoma.
Circulating Cell-Free DNA Methylation Profiling Enables Detection, Distinction, and Estrogen Receptor Status Classification of Advanced Breast Cancer.
A pan-cancer single-cell analysis of intratumoral copy number diversity and evolution.
Φ-Space ST: A platform-agnostic method to identify cell states in spatial transcriptomics studies.
Analysis of cell-free DNA in lymphomas: from sample collection to genotyping and minimal residual disease monitoring.
Tubal epithelial alterations: evolving concepts.
Molecular residual disease (MRD) testing: advancing clinical decision-making in breast cancer.

JAMA. 2026 Jun 08.

ESGO Statements on Opportunistic Salpingectomy for Prevention of Tubo-Ovarian Carcinoma.

Karolina Afors, Ertan Saridogan.

DOI: https://doi.org/10.1001/jama.2026.5831
Cancer Res. 2026 Jun 10.

Circulating Cell-Free DNA Methylation Profiling Enables Detection, Distinction, and Estrogen Receptor Status Classification of Advanced Breast Cancer.

Sasha C Main, Mitchell J Elliott, Althaf Singhawansa, Jinfeng Zou, Yong Zeng, Nicholas Cheng, Celeste Yu, John F Hilton, Philip Awadalla, Housheng H He, Philippe L Bedard, Mathieu Lupien, Scott V Bratman, David W Cescon.

The management of metastatic breast cancer (mBC) relies on tissue-based immunohistochemical subtypes. However, biopsies are invasive, may not capture metastatic heterogeneity, and subtypes can change over time under treatment pressure. Here, we developed cell-free DNA (cfDNA) methylation signatures for minimally invasive BC detection, distinction, and estrogen receptor (ER) status classification. Peripheral blood plasma methylomes were analyzed from 79 patients with mBC spanning ER+/HER2- (n=45), HER2+ (n=13), and triple-negative BC (TNBC; n=21). To derive tissue-informed BC and ER-specific features, public 450K methylation array data (n=9730) were leveraged, and features were selected using generalized linear models via elastic net regularization (GLMnet) with cross-validation. The tissue-informed features were translated to cell-free methylated DNA immunoprecipitation and sequencing (cfMeDIP-seq), and the final signatures were validated across a compendium of cfMeDIP-seq profiles (n=713) spanning over ten cancer types. Across training, validation, and external test cohorts, the signatures demonstrated high accuracy for BC detection versus controls, distinction from multiple other malignancies, and ER status classification. Performance generalized across independent cfMeDIP-seq cohorts and reflected tumor fraction. The sensitivity was reduced in samples with low tumor fractions and bone-only disease, while remaining informative for typical tumor fractions observed in the metastatic setting. Promoter-proximal signature regions provided biological insight into tumor phenotypes. This tissue-anchored, platform-translatable framework demonstrates the feasibility of accurate, reproducible cfDNA methylation-based molecular classification in mBC.

DOI: https://doi.org/10.1158/0008-5472.CAN-26-0076
Cancer Discov. 2026 Jun 08.

A pan-cancer single-cell analysis of intratumoral copy number diversity and evolution.

Hanghui Ye, Thomas O McDonald, Reem Elghaish, Emi Sei, Darlan Conterno Minussi, Min Hu, Shanshan Bai, Chenling Tang, Junke Wang, Kaile Wang, Robert J Downey, Anna Casasent, Michael D Nicholson, Hui Chen, Franziska Michor, Nicholas E Navin.

Aneuploidy is a hallmark of human tumors. While patient-level copy number alteration (CNA) differences have been investigated extensively in large cohorts, their intratumoral heterogeneity remains understudied. Here, we conducted a pan-cancer analysis of 94 human tumors at single cell resolution, representing seven cancer types: bladder, breast, colon, glioblastoma, kidney, lung, and ovarian. Single-cell copy number profiling was used to analyze 62,646 aneuploid cells, in addition to bulk exome sequencing of most patients and single-nucleus RNA-seq of 6 samples. In many cancer types, increased subclonal diversity was associated with higher CNA burden, whole genome doubling, TP53 mutations, and increased geographic diversity. Cancer cells from each patient shared a set of truncal CNAs, suggesting evolution from a single ancestral cell. Many tumors accumulated CNAs in bursts of evolution, suggesting that punctuated evolution is common in diverse cancer types. This study greatly improves our knowledge of intratumoral chromosome diversity across human cancers.

DOI: https://doi.org/10.1158/2159-8290.CD-25-0964
Cell Rep Methods. 2026 Jun 12. pii: S2667-2375(26)00183-9. [Epub ahead of print] 101483

Φ-Space ST: A platform-agnostic method to identify cell states in spatial transcriptomics studies.

Jiadong Mao, Jarny Choi, Kim-Anh Lê Cao.

  We introduce Φ-Space ST, a platform-agnostic method to identify continuous cell states in spatial transcriptomics (ST) data using multiple scRNA-seq references. For ST with supercellular resolution, Φ-Space ST achieves interpretable cell-type deconvolution with significantly faster computation. For subcellular resolution, Φ-Space ST annotates cell states without cell segmentation, leading to highly insightful spatial niche identification. Φ-Space ST harmonizes annotations derived from multiple scRNA-seq references and provides interpretable characterizations of disease cell states by leveraging healthy references. We validate Φ-Space ST in four case studies involving CosMx, Visium, Xenium, and Stereo-seq platforms for various cancer tissues. Our method revealed niche-specific enriched cell types and distinct cell-type co-presence patterns that distinguish tumor from non-tumor tissue regions. These findings highlight the potential of Φ-Space ST as a robust and scalable tool for ST data analysis for understanding complex tissues and pathologies.

Keywords:  CP: cancer biology; CP: computational biology; cell states; cell type deconvolution; spatial niches; spatial transcriptomics

DOI:  https://doi.org/10.1016/j.crmeth.2026.101483
Blood Adv. 2026 Jun 12. pii: bloodadvances.2024015609. [Epub ahead of print]

Analysis of cell-free DNA in lymphomas: from sample collection to genotyping and minimal residual disease monitoring.

Deborah Piffaretti, Chiara Consoli, Davide Rossi.

Circulating tumor DNA (ctDNA) is increasingly investigated in lymphomas because it enables non-invasive molecular profiling, longitudinal assessment of clonal evolution, and quantification of minimal residual disease (MRD), which reflects residual tumor burden and treatment response and serves as a clinically validated prognostic biomarker. The clinical utilities of ctDNA include supporting diagnosis, enabling early detection of relapse, and resolving ambiguous imaging findings. Current approaches for ctDNA assessment in lymphomas include droplet digital PCR, immunoglobulin clonotype sequencing, hybrid-capture next-generation sequencing with unique molecular identifiers or duplex barcoding, and phased sequencing. Establishing ctDNA as a clinical-grade assay requires rigorous quality control and standardization across all technical steps, from blood collection and plasma processing to cfDNA extraction, quantification, and analytically validated genotyping and MRD measurement. Large prospective trials and international standardization efforts are underway to define ctDNA-based MRD assessment as a reproducible and clinically actionable tool in lymphoma care. In this review, we outline key pre-analytical and analytical workflows for ctDNA assessment in lymphomas and discuss unresolved challenges and future directions in the field.

DOI: https://doi.org/10.1182/bloodadvances.2024015609
J Gynecol Oncol. 2026 May 27.

Tubal epithelial alterations: evolving concepts.

Kei Koyama, Daichi Maeda, Akiteru Goto.

  The fallopian tube has emerged as a central organ in the pathogenesis of ovarian cancer, particularly high-grade serous carcinoma (HGSC). Detailed histopathological and molecular analyses have revealed a diverse spectrum of tubal epithelial alterations with varying malignant potentials. This review outlines key lesions including secretory cell outgrowth (SCOUT), p53 signature, serous tubal intraepithelial lesion (STIL), serous tubal intraepithelial carcinoma (STIC), β-catenin signatures, endometrioid tubal intraepithelial neoplasia, and papillary tubal hyperplasia (PTH). The p53 signature, STIL, and STIC are changes originating from secretory cells with underlying TP53 alterations. However, recent findings suggest that these lesions do not necessarily represent a continuous sequence in terms of risk of progression to HGSC. Advances in molecular biology have enabled the estimation of malignant potential of individual lesions. SCOUTs, particularly Type II are thought to be precursors of endometrioid carcinoma. While SCOUTs are frequently observed in the general population, endometrioid carcinoma of the fallopian tube remains extremely rare. PTH has traditionally been regarded as a reactive phenomenon; however morphological and molecular overlaps with low-grade serous carcinoma have recently been suggested. These findings underscore the complexity and heterogeneity of tubal epithelial alterations and suggest that not all lesions follow a linear tumorigenic sequence. Continued integration of morphological, molecular, and spatial analyses will be essential for refining our understanding of tubal pathology and its contribution to gynecological carcinogenesis.

Keywords:  Beta Catenin; Tumor Suppressor Protein p53; sFallopian Tubes

DOI:  https://doi.org/10.3802/jgo.2026.37.e121
Clin Adv Hematol Oncol. 2026 Jun;24(4 Suppl 4): 1-16

Molecular residual disease (MRD) testing: advancing clinical decision-making in breast cancer.

Jason A Mouabbi, Marla D Lipsyc-Sharf, Fengting Yan.

Circulating tumor DNA (ctDNA) is emerging as a clinically meaningful biomarker across multiple solid tumors, including breast cancer. Advances in personalized, tumor-informed whole-genome sequencing have enabled highly sensitive detection of ctDNA, allowing for more precise assessment of tumor burden. Across treatment settings, ctDNA testing has demonstrated consistent prognostic value in patients with breast cancer. In the neoadjuvant setting, ctDNA status is strongly prognostic at baseline and following completion of therapy. After definitive surgery, detection of molecular residual disease (MRD) by ctDNA testing is associated with a marked increased risk of recurrence, with positive predictive values approaching 100% and a lead time of approximately 13.5 months over conventional approaches. These data support the potential role of ctDNA testing as an adjunct to current surveillance strategies, with the aim of identifying recurrence before the onset of significant clinical symptoms. Although ctDNA results are not yet used to guide treatment modification outside of established standards of care, the field is advancing rapidly. Multiple ongoing prospective, interventional trials are evaluating MRDguided therapeutic strategies, and emerging evidence suggests that ctDNA may ultimately help individualize adjuvant therapy-either by identifying patients who may safely de-escalate treatment or by signaling when escalation could be beneficial. In the metastatic setting, ctDNA testing can complement radiographic assessment by providing an additional measure of treatment response, particularly in patients with nonmeasurable or difficult-to-visualize disease. Across all settings, ctDNA testing is most informative when performed longitudinally, enabling assessment of dynamic changes over time. Although baseline ctDNA testing provides valuable prognostic information, its absence at this time point or at diagnosis does not limit the utility of ctDNA assessment at subsequent time points.