Details

Autor(en) / Beteiligte

• Cho, Junhun
• Ahn, Soomin
• Son, Dae‐Soon
• Kim, Nayoung KD
• Lee, Ki‐Wook
• Kim, Seungtae
• Lee, Jeeyun
• Park, Se Hoon
• Park, Joon Oh
• Kang, Won Ki
• An, Ji Yeong
• Choi, Min Gew
• Lee, Jun‐Ho
• Sohn, Tae Sung
• Bae, Jae Moon
• Kim, Sung
• Kim, Kyoung‐Mee

Titel

Bridging genomics and phenomics of gastric carcinoma

Ist Teil von

• International journal of cancer, 2019-11, Vol.145 (9), p.2407-2417

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2019

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Genetic alterations are the starting point leading to numerous changes in clinical and pathologic features (phenotypes) of individual cancers; however, their inter‐relationships in gastric cancers (GC) are unclear. We performed massive parallel sequencing of 381 cancer‐related genes and compared the results with clinical and pathologic findings in 330 GC. High tumor mutation burden (TMB) accounted for 11% of GC (n = 37) and all 19 MSI‐H GCs were high TMB. High TMB was significantly more frequent in intestinal‐type by Lauren, tumor with higher host cellular immune response, earlier AJCC stage and favorable prognosis. The most significantly mutated genes were TP53 (54%), ARID1A (23%), CDH1 (22%), PIK3CA (12%), RNF43 (10%) and KRAS (9%). For receptor tyrosine kinases, amplifications detected by immunohistochemistry were higher than sequencing (HER2, 9.1% vs. 5.8%; EGFR, 11.2% vs. 6.1%; FGFR2, 4.6% vs. 3.9%, c‐MET, 3.4% vs. 0.9%). PTEN protein loss (22%) correlated well with underlying PTEN alterations while ATM loss (27%) was not significantly correlated with genetic alterations of ATM. p53 protein expression predicted alterations of TP53 with high sensitivity (97.8%) and low (15.9%) specificity. The poorly cohesive histology/CDH1‐mutant GC subgroup showed the worst survival (p < 0.001). PD‐L1 expression was significantly associated with MSI‐H, MLH1 loss, ATM loss, MET positivity, higher host immune response, and genetic alterations of ARID1A, BRD3, PIK3CA, KRAS, MAP3K13, CDH2, PTEN and ESR1. The merged clinical, pathology and genomics of GC provide a better understanding of GC and new insights into the treatment of GC. What's new? Genetic alterations are the starting point of numerous changes in clinical and pathologic features (phenotypes) of individual cancers; however, their interrelationships in gastric cancers (GC) remain unclear. In this study correlating clinical, pathologic, and genomics data in 330 GC patients, high tumor mutation burden (TMB) accounted for 11% of cases and was significantly more frequent in intestinal‐type GC, tumors with higher host immune response, earlier cancer stage, and favorable prognosis. PD‐L1 expression was significantly associated with MSI‐H, higher host immune response, and high TMB. The results provide a better understanding of GC and serve as a baseline for precision oncology.