CapTCR-seq: hybrid capture for T-cell receptor repertoire profiling.

Mature T-cell lymphomas consisting of an expanded clonal population of T cells that possess common rearrangements of the T-cell receptor (TCR) encoding genes can be identified and monitored using molecular methods of T-cell repertoire analysis. We have developed a hybrid-capture method that enriches DNA sequencing libraries for fragments encoding rearranged TCR genes from all 4 loci in a single reaction. We use this method to describe the TCR repertoires of 63 putative lymphoma clinical isolates, 7 peripheral blood mononuclear cell (PBMC) populations, and a collection of tumor infiltrating lymphocytes.

Landscape of genomic alterations in high-grade serous ovarian cancer from exceptional long- and short-term survivors.

Background: Patients diagnosed with high-grade serous ovarian cancer (HGSOC) who received initial debulking surgery followed by platinum-based chemotherapy can experience highly variable clinical responses. A small percentage of women experience exceptional long-term survival (long term (LT), 10+ years), while others develop primary resistance to therapy and succumb to disease in less than 2 years (short term (ST)). To improve clinical management of HGSOC, there is a need to better characterize clinical and molecular profiles to identify factors that underpin these disparate survival responses.

Somatic BRCA1/2 Recovery as a Resistance Mechanism After Exceptional Response to Poly (ADP-ribose) Polymerase Inhibition.

Purpose Durable and long-term responses to the poly (ADP-ribose) polymerase inhibitor olaparib are observed in patients without BRCA1/2 mutations. However, beyond BRCA1/2 mutations, there are no approved biomarkers for olaparib in high-grade serous ovarian cancer (HGSOC). To determine mechanisms of durable response and resistance to olaparib therapy, we performed an analysis of HGSOC tumors from three patients without germline BRCA1/2 mutations who experienced exceptional responses to olaparib.

The genomic landscape of schwannoma.

Schwannomas are common peripheral nerve sheath tumors that can cause debilitating morbidities. We performed an integrative analysis to determine genomic aberrations common to sporadic schwannomas. Exome sequence analysis with validation by targeted DNA sequencing of 125 samples uncovered, in addition to expected NF2 disruption, recurrent mutations in ARID1A, ARID1B and DDR1.

Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer.

Sustained expression of the estrogen receptor-α (ESR1) drives two-thirds of breast cancer and defines the ESR1-positive subtype. ESR1 engages enhancers upon estrogen stimulation to establish an oncogenic expression program. Somatic copy number alterations involving the ESR1 gene occur in approximately 1% of ESR1-positive breast cancers, suggesting that other mechanisms underlie the persistent expression of ESR1.

Long-range PCR and next-generation sequencing of BRCA1 and BRCA2 in breast cancer.

Individuals and families carrying mutations in BRCA1 and BRCA2 (BRCA1/2) have a markedly elevated risk of developing breast and ovarian cancers. The first-generation of BRCA1/2 mutation analysis targeted only the coding exons and has implicated protein-truncating mutations (indel, nonsense) in BRCA1/2 inactivation. Recently, heritable breast cancers have also been attributed to other exonic mutations (missense, silent) and mutations in introns and untranslated regions.

Application of post-surgical stimulated thyroglobulin for radioiodine remnant ablation selection in low-risk papillary thyroid carcinoma.

Background: We present our ongoing experience in the use of postsurgical stimulated serum thyroglobulin (Stim-Tg) to assist in radioiodine remnant ablation (RRA) decision-making.

Methods: Patients with low-risk well-differentiated thyroid carcinoma (WDTC) with undetectable anti-Tg antibodies were prospectively followed after total thyroidectomy and therapeutic central compartment neck dissection, when indicated.Stim-Tg was performed 3 months postoperatively and used to base RRA selection.

Influence of age and primary tumor size on the risk for residual/recurrent well-differentiated thyroid carcinoma.

Background: Though age and primary tumor size predict cancer-specific survival in well-differentiated thyroid carcinoma (WDTC), their influence on residual/recurrent disease has not been elucidated.

Methods: In a retrospective study, residual/recurrent disease was defined by the surrogate outcome of positive (>or=2 microg/L) follow-up stimulated thyroglobulin after surgery and radioactive remnant ablation. Age, primary tumor size, and clinical staging systems were examined in the context of stimulated thyroglobulin outcome.

Prognostic value of postsurgical stimulated thyroglobulin levels after initial radioactive iodine therapy in well-differentiated thyroid carcinoma.

Background: In well-differentiated thyroid carcinoma, predictors of future positivity of stimulated thyroglobulin (>2 microg/L) after initial radioactive iodine treatment are not known.

Methods: In a retrospective study, we used logistic regression analysis to determine whether postoperative stimulated thyroglobulin measurements and pathologic stage independently predict future stimulated thyroglobulin positivity.

Results: We followed 141 patients with well-differentiated thyroid carcinoma for a median of 35 months; follow-up stimulated thyroglobulin measurements were positive in 20.