Mutations in Epigenetic Regulation Genes in Gastric Cancer

We have performed mutational profiling of 25 genes involved in epigenetic processes on 135 gastric cancer (GC) samples. In total, we identified 79 somatic mutations in 49/135 (36%) samples. The minority (n = 8) of mutations was identified in DNA methylation/demethylation genes, while the majority (n = 41), in histone modifier genes, among which mutations were most commonly found in KMT2D and KMT2C. Somatic mutations in KMT2D, KMT2C, ARID1A and CHD7 were mutually exclusive (p = 0.038). Mutations in ARID1A were associated with distant metastases (p = 0.03). The overall survival of patients in the group with metastases and in the group with tumors with signet ring cells was significantly reduced in the presence of mutations in epigenetic regulation genes (p = 0.036 and p = 0.041, respectively). Separately, somatic mutations in chromatin remodeling genes correlate with low survival rate of patients without distant metastasis (p = 0.045) and in the presence of signet ring cells (p = 0.0014). Our results suggest that mutations in epigenetic regulation genes may be valuable clinical markers and deserve further exploration in independent cohorts.

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Somatic mutations in epigenetic regulation genes detected by NGS in gastric tumors

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2020.06.75-76 ◽

2020 ◽

pp. 75-76

Author(s):

М.В. Немцова ◽

А.И. Калинкин ◽

Е.Б. Кузнецова ◽

Е.А. Алексеева ◽

И.В. Буре ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Epigenetic Regulation ◽

Somatic Mutations ◽

Prognostic Markers ◽

Epigenetic Mechanisms ◽

Clinical Marker ◽

Mutational Profiling ◽

Cell Life ◽

First Results

Эпигенетические механизмы регулируют структуру хроматина и создают устойчивые закономерности экспрессии генов в процессе жизни клеток. Нарушение эпигенетической регуляции играет значительную роль в канцерогенезе, инвазии, рецидивировании и метастазировании опухолей и может служить полезным клиническим маркером. Мутационное профилирование генов эпигенетической регуляции в опухолевых образцах рака желудка позволит определить новые клинические и прогностические маркеры и дополнительные таргеты для лечения пациентов. В статье представлены первые результаты исследования соматических мутаций в генах эпигенетической регуляции, проведенного методом NGS. Epigenetic mechanisms regulate chromatin structure and create stable patterns of gene expression during cell life. Violation of epigenetic regulation plays a significant role in carcinogenesis, invasion, recurrence and metastasis of tumors, and can serve as a useful clinical marker. Mutational profiling of epigenetic regulation genes in tumor samples of gastric cancer will allow us to identify new clinical and prognostic markers and additional targets for the treatment of patients with gastric cancer. This article presents the first results of a study of somatic mutations in the epigenetic regulation genes carried out using NGS.

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Polyserositis revealing a signet ring cells gastric adenocarcinoma in a 27 years old male patient: A case report.

10.21203/rs.3.rs-844525/v1 ◽

2021 ◽

Author(s):

Zahid Talibi Alaoui ◽

Salah Eddine Youbi ◽

Fatima Ihbibane ◽

Hind Rachidi ◽

Fatima Ezzahra Hazmiri ◽

...

Keyword(s):

Gastric Cancer ◽

Emergency Department ◽

Case Report ◽

Clinical Improvement ◽

Gastric Adenocarcinoma ◽

Male Patient ◽

Signet Ring Cells ◽

Signet Ring

Abstract Gastric cancer remains one of the most common and deadly cancers worldwide, especially among old males. It is rare in the younger population (< 30 years old). We describe the case of a 27 years old male patient, presenting to the emergency department, with exsudative polyserositis, initially misdiagnosed and treated as a multifocal tuberculosis with no clinical improvement, later revealing a metastatic signet ring cells gastric adenocarcinoma.

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A case of metastatic invasive lobular carcinoma of the greater omentum with signet ring cells in the ascitic fluid, which was difficult to distinguish from gastric cancer

The Journal of the Japanese Society of Clinical Cytology ◽

10.5795/jjscc.60.284 ◽

2021 ◽

Vol 60 (5) ◽

pp. 284-288

Author(s):

Seiya MIZUGUCHI ◽

Hiroshi MINATO ◽

Ayako KUROKAWA ◽

Hiroto ONISHI ◽

Yoshiyuki SHINYA ◽

...

Keyword(s):

Gastric Cancer ◽

Ascitic Fluid ◽

Invasive Lobular Carcinoma ◽

Lobular Carcinoma ◽

Greater Omentum ◽

Signet Ring Cells ◽

Signet Ring

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Prognostic Significance of Signet Ring Gastric Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2012.42.6635 ◽

2012 ◽

Vol 30 (28) ◽

pp. 3493-3498 ◽

Cited By ~ 97

Author(s):

Sharven Taghavi ◽

Senthil N. Jayarajan ◽

Adam Davey ◽

Alliric I. Willis

Keyword(s):

United States ◽

Gastric Cancer ◽

Alaska Native ◽

Prognostic Significance ◽

Distant Metastases ◽

Tumor Grade ◽

The United States ◽

Signet Ring Cell ◽

Signet Ring ◽

Worse Prognosis

Purpose Studies in Asia have questioned the dictum that signet ring cell carcinoma (SRC) has a worse prognosis than other forms of gastric cancer. Our study determined differences in presentation and outcomes between SRC and gastric adenocarcinoma (AC) in the United States. Patients and Methods The National Cancer Institute Surveillance, Epidemiology, and End Results database was reviewed for SRC and AC from 2004 to 2007. Results We reviewed 10,246 cases of patients with gastric cancer, including 2,666 of SRC and 7,580 of AC. SRC presented in younger patients (61.9 v 68.7 years; P < .001) and less often in men (52.7% v 68.7%; P < .001). SRC patients were more frequently black (11.3% v 10.9%), Asian (16.4% v 13.2%), American Indian/Alaska Native (0.9% v 0.8%), or Hispanic (23.3% v 14.0%; P < .001). SRC was more likely to be stage T3-4 (45.8% v 33.3%), have lymph node spread (59.7% v 51.8%), and distant metastases (40.2% v 37.6%; P < .001). SRC was more likely to be found in the lower (30.7% v 24.2%) and middle stomach (30.6% v 20.7%; P < .001). Median survival was not different between the two (AC, 14.0 months v SRC, 13.0 months; P = .073). Multivariable analyses demonstrated SRC was not associated with mortality (hazard ratio [HR], 1.05; 95% CI, 0.96 to 1.11; P = .150). Mortality was associated with age (HR, 1.01; 95% CI, 1.01 to 1.02; P < .001), black race (HR, 1.10; 95% CI, 1.01 to 1.20; P = .026), and tumor grade. Variables associated with lower mortality risk included Asian race (HR, 0.83; 95% CI, 0.77 to 0.91; P < .001) and surgery (HR, 0.37; 95% CI, 0.34 to 0.39; P < .001). Conclusion In the United States, SRC significantly differs from AC in extent of disease at presentation. However, when adjusted for stage, SRC does not portend a worse prognosis.

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Krukenberg's Tumor as an Incidental Finding in a Full-Term Pregnancy: A Case Report

10.20944/preprints202006.0140.v1 ◽

2020 ◽

Author(s):

Orlando Andres Nunez-Isaac ◽

Felipe Mendoza-Rosado ◽

Katheryn Lopez-Arjona ◽

Alan Espinosa-Marron ◽

Fernando Davila-Martinez

Keyword(s):

Gastric Cancer ◽

Pregnant Woman ◽

Incidental Finding ◽

Abdominal Cavity ◽

Vena Cava ◽

Krukenberg Tumor ◽

Mri Findings ◽

Signet Ring Cells ◽

Uncommon Presentation ◽

Signet Ring

BACKGROUND Krukenberg tumor is a rare metastatic tumor of the ovary with characteristic histopathological features known as signet-ring cells. It usually presents in women around 45 years of age, however, we present an uncommon case in a 38-year-old pregnant woman. We report this case because of the unusual findings, the uncommon presentation in this younger age bracket, its diagnostic challenge, and poor prognosis. CASE PRESENTATION We describe an unusual case of a young woman with a history of painful vaginal bleeding at 13 weeks of pregnancy and treated for abruptio placentae. In her routine prenatal visit at week 20 of pregnancy, she was found to have a uterine fundus greater than her gestational age and referred to the hospital to discard polyhydramnios. At her admission a pelvic ultrasound was performed with normal findings of a 25 weeks pregnancy, also showing bilateral enlarged ovaries with heterogeneous echogenicity. The MRI showed a left tumoral lesion with dimensions of 22.1 x 13.6 x 16.3 cm, with lobulated regular contours with displacement of peripheral structures and mild compression of the bladder, the left ureter, and the inferior vena cava. The lesion was heterogeneous with irregular borders. The patient was programmed for a cesarean section; during the operation, the abdominal cavity showed bilateral tumors compatible with MRI findings, the ovarian tumors were sent to pathology and the results showed poorly differentiated mucinous adenocarcinoma (WHO III) with extensive signet-ring cells, an indicative of Krukenberg tumor. CONCLUSION: The case presented is rare due to its presentation in a pregnant woman without identifiable risk factors for gastric cancer. The incidental finding suggests the pregnancy masked the clinical presentation of gastric cancer, and the rapid deterioration of the patient is consistent with the aggressiveness described in the literature. The limited descriptions of this neoplasm in our country and the torpid evolution of this case highlight the importance of further studies of this cancer in Mexico.

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Chemoradiotherapy Is Inferior to Chemotherapy Alone in Adjuvant Setting for Signet Ring Cell Containing Gastric Cancer

Frontiers in Oncology ◽

10.3389/fonc.2020.570268 ◽

2020 ◽

Vol 10 ◽

Author(s):

Yue-Ting Zhu ◽

Xin-Zu Chen ◽

Ye Chen ◽

Yu-Wen Zhou ◽

Lian-Sha Tang ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Adjuvant Chemotherapy ◽

Signet Ring Cell ◽

Adjuvant Chemoradiotherapy ◽

Signet Ring Cells ◽

D2 Gastrectomy ◽

Vessel Invasion ◽

Signet Ring ◽

Ring Cell

BackgroundSignet ring cell containing gastric cancer (SRCGC) is a rare subtype of gastric cancer, and its adjuvant therapy is based on general gastric cancer. However, the effectiveness of radiotherapy for those SRCGC patients remains unknown.PurposeThe purpose of the study was to analyze whether the addition of radiotherapy to adjuvant chemotherapy (CT) can benefit survival in resected SRCGC patients.MethodsPatients with SRCGC, who underwent D2 gastrectomy followed by adjuvant chemotherapy or chemoradiotherapy (CRT), were retrospectively collected. According to the proportion of signet ring cells, patients were histologically classified as pure SRCGC (pSRCGC) containing 100% of signet ring cells, mixed SRCGC (mSRCGC) containing >50% of signet ring cells, and contaminated SRCGC (cSRCGC) containing <50% of signet ring cells. Among the 272 patients, 156 were treated by CT alone and 116 by CRT. The primary endpoint was 3-year overall survival rate (3-year OS rate).ResultsWith a median follow-up of 80.5 months, the 3-year OS rate was significantly higher in the CT group (70.5% vs. 58.6%, HR = 0.633, P = 0.017) compared with CRT group. Three independent characteristics were predictive of a poor overall survival: CRT treatment (P = 0.019), tumor size ≥5 cm (P < 0.001), and the presence of vessel invasion (P = 0.009). Subgroup analyses showed CRT significantly impaired prognosis in SRCGC patients in the cSRCGC subset, as well as lesions located in lower-middle sites, subtotal gastrectomy, male, <60 year, and no vessel invasion. Peritoneal was the most common recurrence site in SRCGC patients. The adverse events leukopenia and neutropenia were more common in the CRT group (P = 0.007).ConclusionsAdjuvant chemoradiotherapy was associated with poor survival compared with adjuvant chemotherapy in SRCGC patients with D2 gastrectomy.

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Trimodal imaging to identify microscopic foci of signet ring cells in hereditary diffuse gastric cancer

Gut ◽

10.1136/gut.2011.239301.407 ◽

2011 ◽

Vol 60 (Suppl 1) ◽

pp. A192-A193 ◽

Cited By ~ 1

Author(s):

Y. C. Lim ◽

I. Debiram ◽

M. O'Donovan ◽

S. Richardson ◽

S. Dwerryhouse ◽

...

Keyword(s):

Gastric Cancer ◽

Hereditary Diffuse Gastric Cancer ◽

Diffuse Gastric Cancer ◽

Signet Ring Cells ◽

Signet Ring

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Adrenal Crisis and Disseminated Intravascular Coagulation Associated With Disseminated Carcinomatosis of the Bone Marrow From Gastric Cancer

10.21203/rs.3.rs-272089/v1 ◽

2021 ◽

Author(s):

Roland Y Lee ◽

Elliott Goldberg ◽

Jozef Malysz ◽

Huili Li ◽

Benjamin Shin ◽

...

Keyword(s):

Gastric Cancer ◽

Bone Marrow ◽

Disseminated Intravascular Coagulation ◽

Adrenal Crisis ◽

Appendicular Skeleton ◽

Metastatic Adenocarcinoma ◽

Signet Ring Cells ◽

Intravascular Coagulation ◽

Signet Ring ◽

Diffuse Sclerosis

Abstract Gastric cancer is the third leading cause of cancer deaths worldwide. Disseminated carcinomatosis of bone marrow (DCBM) originating from gastric cancer is rare and associated with poor prognosis. We present the first reported case of gastric adenocarcinoma with DCBM leading to concomitant disseminated intravascular coagulation (DIC) and adrenal crisis refractory to treatment. Computerized tomography of the chest, abdomen and pelvis showed diffuse sclerosis of the axial and proximal appendicular skeleton, suggestive of metastatic disease. Bone marrow biopsy demonstrated infiltrative signet ring cells, consistent with metastatic adenocarcinoma from gastric primary. Laboratory tests showed severe anemia, thrombocytopenia, and coagulopathy, compatible with DIC.

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Management of synchronous Krukenberg tumors from gastric cancer: A single-center experience.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15563 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15563-e15563

Author(s):

Pengfei Yu ◽

Ling Huang ◽

Yian Du ◽

Xiangdong Cheng

Keyword(s):

Gastric Cancer ◽

Peritoneal Carcinomatosis ◽

Survival Benefit ◽

Clinicopathological Characteristics ◽

Signet Ring Cells ◽

Ovarian Metastases ◽

Single Center Experience ◽

Signet Ring ◽

Krukenberg Tumors ◽

Gastric Cancer Patients

e15563 Background: Whether metastasectomy improves prognosis of gastric cancer patients with ovarian metastases (Krukenberg tumors) is not clear. In this study, we examined the survival benefit of metastasectomy combined with chemotherapy for treatment of synchronous Krukenberg tumors from gastric cancer and identified the prognostic factors. Methods: The subjects of this study were patients diagnosed as synchronous Krukenberg tumors of gastric origin in the period between December 2004 and December 2015. Patients were classified in accordance with treatment modality: metastasectomy group (metastasectomy combined with chemotherapy) and non-metastasectomy group (chemotherapy alone). Clinicopathological characteristics together with treatment records were investigated in detail and their relationship with survival outcomes was examined. Results: Out of a total of 103 patients, 54 (52.4%) underwent metastasectomy of Krukenberg tumors while 49 (47.6%) patients had chemotherapy alone. Overall survival (OS) in the metastasectomy group was significantly longer than that in the non-metastasectomy group (18.9 months vs. 12.4 months, respectively; P < 0.001). Metastasectomy (hazard ratio [HR] 0.486; 95% confidence interval [CI] 0.323–0.729; P < 0.001), signet ring cells (HR 1.938; 95% CI 1.182–3.175; P = 0.009), peritoneal carcinomatosis (HR 1.934; 95% CI 1.230–3.049; P = 0.004), expression of estrogen receptor-β (ER-β) (HR 0.404; 95% CI 0.251–0.648; P < 0.001), and progesterone receptor (PR) (HR 0.496; 95% CI 0.301–0.817; P < 0.001) were independent predictors of OS. Conclusions: Metastasectomy combined with chemotherapy showed an association with survival benefit in patients with synchronous Krukenberg tumors from gastric cancer. Metastasectomy, expression of ER-β and PR, peritoneal carcinomatosis, and signet ring cells were independent predictors of survival. Further prospective studies are warranted.

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