Lymphoma-associated mutations in autoreactive memory B cells of patients with Sjögren's syndrome

We recently demonstrated that normal memory B lymphocytes carry a substantial number of de novo mutations in the genome. Here, we performed exome-wide somatic mutation analyses of bona fide autoreactive rheumatoid factor (RF)-expressing memory B cells retrieved from patients with Sjӧgren's syndrome (SS). The amount and repertoire of the de novo exome mutations of RF B cells were found to be essentially different from those detected in healthy donor memory B cells. In contrast to the mutation spectra of normal B cells, which appeared random and non-selected, the mutations of the RF B cells were greater in number and enriched for mutations in genes also found mutated in B-cell non-Hodgkin lymphomas. During the study, one of the SS patients developed a diffuse large B-cell lymphoma (DLBCL) out of an RF clone that was identified 2 years earlier in an inflamed salivary gland biopsy. The successive oncogenic events in the RF precursor clone and the DLBCL were assessed. In conclusion, our findings of enhanced and selected genomic damage in growth-regulating genes in RF memory B cells of SS patients together with the documented transformation of an RF-precursor clone into DLBCL provide unique novel insight into the earliest stages of B-cell derailment and lymphomagenesis.</p

Lymphoma-associated mutations in autoreactive memory B cells of patients with Sjögren's syndrome

We recently demonstrated that normal memory B lymphocytes carry a substantial number of de novo mutations in the genome. Here, we performed exome-wide somatic mutation analyses of bona fide autoreactive rheumatoid factor (RF)-expressing memory B cells retrieved from patients with Sjӧgren's syndrome (SS). The amount and repertoire of the de novo exome mutations of RF B cells were found to be essentially different from those detected in healthy donor memory B cells. In contrast to the mutation spectra of normal B cells, which appeared random and non-selected, the mutations of the RF B cells were greater in number and enriched for mutations in genes also found mutated in B-cell non-Hodgkin lymphomas. During the study, one of the SS patients developed a diffuse large B-cell lymphoma (DLBCL) out of an RF clone that was identified 2 years earlier in an inflamed salivary gland biopsy. The successive oncogenic events in the RF precursor clone and the DLBCL were assessed. In conclusion, our findings of enhanced and selected genomic damage in growth-regulating genes in RF memory B cells of SS patients together with the documented transformation of an RF-precursor clone into DLBCL provide unique novel insight into the earliest stages of B-cell derailment and lymphomagenesis.</p

Prospective longitudinal study on fear of cancer recurrence in patients newly diagnosed with head and neck cancer:Course, trajectories, and associated factors

Background: This study assessed the course of fear of cancer recurrence (FCR) in patients newly diagnosed with head and neck cancer (HNC), identified FCR trajectories and factors associated with FCR trajectories. Methods: Six hundred and seventeen HNC patients from the NET-QUBIC cohort study completed the Cancer Worry Scale-6 at diagnosis, 3 and 6 months post-treatment. FCR trajectories were identified using Latent Class Growth Analysis. Associations were explored between FCR trajectories and baseline demographic and medical variables, coping and self-efficacy. Results: Overall, FCR decreased slightly between baseline and 3 months post-treatment and remained stable up to 6 months. Two FCR trajectories were identified: “high stable” (n = 125) and “low declining” (n = 492). Patients with high stable FCR were younger, reported more negative adjustment, passive coping, and reassuring thoughts, and less avoidance. Conclusions: The majority of HNC patients have low declining FCR after diagnosis, but one in five patients experience persistent high FCR up to 6 months post-treatment