Mutational landscape and clonal diversity of pulmonary adenoid cystic carcinoma

Abstract

Pulmonary adenoid cystic carcinoma is a rare and indolent lung malignancy, characterized by a protracted but unpredictable growth behavior. Currently, the treatment of PACC relies on surgery and local radiotherapy. However, treatment options for advanced PACC patients are limited. A larger number of studies demonstrated that advanced PACC patients obtained limited benefit from chemotherapy. Moreover, only a few case reports revealed PACC patients were candidates for target therapy. Therefore, there is an urgent need to develop novel therapies. Due to its rareness, its mutational landscape remains largely elusive. In this study, we performed capture-based ultra-deep sequencing on multiregional surgical specimens obtained from 8 PACC patients using a panel consisting of 295 cancer-related genes. Our data revealed distinctive mutational spectrum of PACC, which differed from non-small cell lung cancer and adenoid cystic carcinomas originated from other anatomical sites. PACC, lacking mutations in a majority of non-small cell lung cancer driver genes, has frequent mutations in genes participating in chromatin remodeling and NOTCH signaling pathway. We also elucidated spatial intra-tumoral heterogeneity, which varied among cases. Most mutations in chromatin remodelers were subclonal. Collectively, our findings elucidated molecular signature associated with PACC and highlighted the potential for epigenetic therapy in this disease.

PD-L1 and PD-L2 Expression Levels Are Low in Primary and Secondary Adenoid Cystic Carcinomas of the Orbit: Therapeutic Implications

“…Occasional tumors focally expressed higher levels of PD-L1 or PD-L2. These results, in conjunction with the overall relatively low mutational burden of ACC, 20,22,28,29 suggest that although a small subset of tumors may have the potential to respond to checkpoint inhibitors, most will not. The CPS for PD-L1, on the other hand, revealed that 57% of tumors had scores of =1, which in clinical practice would indicate that up to 57% could be eligible for treatment with checkpoint inhibitors.…”

A Delicate Surgical Resection to Treat a Proximal Pulmonary Adenoid Cystic Carcinoma

“…Developed surgical and anesthesiological procedures would make even wide tumors resectable. Contraindications to surgery include mediastinal lymph nodes, vascular involvement, tracheal invasion for more than 50% of its length, and distant metastases [ 10 ].…”

Classification of gastric cancer by EBV status combined with molecular profiling predicts patient prognosis

“…DNA concentration was measured using the Qubit dsDNA HS Assay kit on a Qubit Fluorometer 3.0 (Life Technologies, Carlsbad, CA, USA). The threshold of input DNA quantity was 200 ng for samples to be processed further for library preparation using the OncoScreen Panel covering 295 key genes (Burning Rock Biotech Ltd, Guangdong, China) as previously described 15,16 . Fragments between 200 and 400 bp were purified by AGEcout AMPure beads (Beckman Coulter, Pasadena, CA, USA).…”