Integrated Molecular and Clinical Profiling of Transformed Splenic Marginal Zone Lymphoma

Already existing and coded tumor biological material and health-related patient data will be retrospectively collected from institutional biobanks and patients' charts or electronic medical records upon receipt of ethical approval. Each patient enrolled in the study will be assigned a unique identification numerical code upon registration in the study. The unique identification code will be used to record health-related data and to label biological samples. Health-related data will be collected by electronic case report form (e-CRF) system. Data quality will be insured by query generation.

Annotated baseline features will include: date of diagnosis, date and tissue type of histological sample collected at diagnosis (spleen and/or bone marrow), age, gender, Eastern Cooperative Oncology Group - Performing Status (ECOG-PS), Ann Arbor stage, Lactate Dehydrogenase (LDH), number and location of extranodal sites, bone marrow involvement and percentage, peripheral blood involvement, bulky disease (\>7 cm), number of nodal sites, B symptoms, hemoglobin, platelets, lymphocytes, beta-2-microglobulin, albumin, Hepatitis C Virus (HCV) infection, serum paraprotein and type.

Annotated follow-up features will include: the date of progression to a disease requiring treatment, type of first line treatment, date of start of the first line treatment, date of progression after first line treatment, date of the second line treatment, type of second line treatment.

Annotated transformation features will include: date of transformation, date and type of histological sample collected at transformation (spleen and/or bone marrow and/or lymph node and/or other site), histological transformation type and relative molecular data (if available), ECOG-PS, Ann Arbor stage, LDH, number and location of extranodal sites, bone marrow involvement and percentage, peripheral blood involvement, bulky disease (\>7 cm), number of nodal sites, B symptoms, hemoglobin, platelets, lymphocytes, beta-2-microglobulin, albumin, serum paraprotein, and type.

Survival features will include the date of death, cause of death, date of last follow-up.

Mutation analysis, immunoglobulin gene rearrangement analysis, copy number aberration analysis, structural variant analysis, and DNA methylation profile will be performed by Next Generation Sequencing (NGS) of genomic DNA extracted from the biological sample available for the analysis. Gene expression will be assessed by NGS of RNA extracted from from the biological sample available for the analysis.

• Prevalence of HT molecular subtypes defined by genetic lesions [Time frame: 30 months: from the end of samples collection to the end of study analysis]
• Prevalence of Histological Transformation (HT) molecular subtypes defined by gene expression [Time frame: 30 months: from the end of samples collection to the end of study analysis]
• Prevalence of HT molecular subtypes defined by genetic methylation profile [Time frame: 30 months: from the end of samples collection to the end of study analysis]
• Prevalence of molecular features in relation with clinical, laboratory and radiological/Positron Emission Tomography (PET) features at SMZL diagnosis and at HT [Time frame: 30 months: from the end of samples collection to the end of study analysis]