Comprehensive Molecular Profiling of Cribriform Tumors: Identification of Recurrent 6q/9q Codeletion and CD38 Expression

Pierre Sohier ¹, Maxime Battistella ², Maxime Mouthon ²

¹CARADERM, French Network of Rare Skin Cancers, Lille, France; Department of Pathology, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre-Université Paris Cité, Paris, France.
²CARADERM, French Network of Rare Skin Cancers, Lille, France; Department of Pathology, Assistance Publique-Hôpitaux de Paris Hôpital Saint-Louis, Institut national de la santé et de la recherche médicale (INSERM) U1342, Université Paris Cité, Paris, France.
³CARADERM, French Network of Rare Skin Cancers, Lille, France; Department of Biopathology, Centre Léon Bérard, Lyon, France; Université de Lyon, Université Claude Bernard Lyon 1, Institut national de la santé et de la recherche médicale (INSERM) U1052, Centre national de la recherche scientifique (CNRS) 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.
⁴CARADERM, French Network of Rare Skin Cancers, Lille, France; Department of Pathology, Assistance Publique-Hôpitaux de Paris, Henri Mondor Hospital, Créteil, France; Paris est Créteil University (UPEC) and Institut national de la santé et de la recherche médicale (INSERM) U955 (Team Ortonne), 8 rue du Général Sarrail, Créteil, France.
⁵CARADERM, French Network of Rare Skin Cancers, Lille, France; Department of Pathology, University Hospital of Bordeaux, Bordeaux, France.
⁶Department of Pathology, Institut Curie, Paris Sciences et Lettres (PSL) University, Paris, France.
⁷Department of Molecular Pathology, Bordeaux University Hospital - Haut Lévêque, Avenue de Haut Lévêque, Pessac, France.
⁸Department of Dermatopathology, St John's institute of Dermatology, Guy's and St Thomas' National Health Service trust, London, United Kingdom.
⁹Laboratoire Aquipath Centre de Dermatopathologie Aquitain, Talence, France.
¹⁰CARADERM, French Network of Rare Skin Cancers, Lille, France; Department of Pathology, Oncopole, Toulouse, France.
¹¹Clinical Cooperation Unit Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹²Department of Biopathology, Centre Léon Bérard, Lyon, France; Université de Lyon, Université Claude Bernard Lyon 1, Institut national de la santé et de la recherche médicale (INSERM) U1052, Centre national de la recherche scientifique (CNRS) 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.
¹³CARADERM, French Network of Rare Skin Cancers, Lille, France; Department of Dermatology, University of Strasbourg, Strasbourg, France.
¹⁴CARADERM, French Network of Rare Skin Cancers, Lille, France; Department of Pathology, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours, France; "Biologie des infections à polyomavirus" team, Université de Tours, Tours, France.
¹⁵CARADERM, French Network of Rare Skin Cancers, Lille, France; Department of Pathology, Assistance Publique - Hôpitaux de Marseille (AP-HM), Timone, Marseille, France; Aix Marseille Univ, Institut national de la santé et de la recherche médicale (INSERM), Marseille Medical Genetics (MMG), Marseille, France.

⁰CARADERM, French Network of Rare Skin Cancers, Lille, France; Department of Pathology, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre-Université Paris Cité, Paris, France.

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc +

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September 14, 2025

View abstract on PubMed

Summary

Cribriform tumors are a distinct skin neoplasm. This study reveals they are a homogeneous molecular entity, characterized by 6q/9q codeletions and CD38 protein expression, indicating an indolent nature.

Area Of Science

Dermatopathology
Oncology
Molecular Biology

Background

Cribriform tumors are distinctive cutaneous adnexal neoplasms with a cribriform growth pattern.
Despite an indolent clinical course, their oncogenic drivers remain unknown.
Previous studies have not fully elucidated their molecular characteristics.

Purpose Of The Study

To provide a novel characterization of cribriform tumors using molecular and gene expression profiling.
To identify novel genetic and protein biomarkers for cribriform tumors.
To determine the molecular distinctiveness of cribriform tumors compared to other adnexal neoplasms.

Main Methods

Whole-transcriptome analysis using RNA sequencing and DNA methylation analysis on 15 cribriform tumor cases.
Copy number variation analysis and fluorescence in situ hybridization (FISH) for genetic alterations.
Gene expression analysis and immunohistochemistry for protein biomarker validation (CD38).

Main Results

Unsupervised clustering confirmed cribriform tumors as a homogeneous molecular entity, distinct from other adnexal neoplasms.
Recurrent 6q/9q codeletions were identified in 7 of 8 tested cases.
Overexpression of CD38 was consistently observed in all cribriform tumors, confirmed by immunohistochemistry.

Conclusions

Cribriform tumors represent a homogeneous group of cutaneous adnexal neoplasms.
Recurrent 6q/9q codeletions and CD38 expression are key molecular characteristics.
These findings support the indolent nature and provide novel biomarkers for cribriform tumors.

Keywords:

6q 9q CD38 adnexal cribriform carcinoma cribriform tumor

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