Double somatic mutations in mismatch repair genes are frequent in colorectal cancer after Hodgkin's lymphoma treatment

Rigter, Lisanne S.; Snæbjörnsson, Pétur; Rosenberg, Efraim H.; Atmodimedjo, Peggy N.; Aleman, Berthe M.P.; Hoeve, Jelle ten; Geurts-Giele, Willemina R.R.; Ravesteyn, T.W. van; Hoeksel, Johan; Meijer, Gerrit A.; Riele, Hein te; Leeuwen, Flora E. van; Dinjens, Winand N.M.; Leerdam, Monique E. van

doi:10.1136/gutjnl-2016-312608

Cited by 31 publications

(43 citation statements)

References 53 publications

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“…15,27 Second, especially in female HL survivors, we detected a high prevalence of serrated lesions and serrated polyposis syndrome. First, neoplastic lesions were more frequently located in the proximal colon in HL survivors in comparison with controls.…”

Section: Discussionmentioning

confidence: 78%

“…15 These mutations could not be associated with a colonic region, sex, or a specific HL treatment. 15 These mutations could not be associated with a colonic region, sex, or a specific HL treatment.…”

Section: Discussionmentioning

confidence: 97%

“…15 Here we report on a predefined interim analysis of a study aimed at comparing the diagnostic yields of a first surveillance colonoscopy in HL survivors and a first screening colonoscopy in the general population. This is related to the lack of knowledge of the natural history and presence of precursor lesions, which may influence surveillance efficacy.…”

Section: Introductionmentioning

confidence: 99%

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High prevalence of advanced colorectal neoplasia and serrated polyposis syndrome in Hodgkin lymphoma survivors

Rigter

Spaander

Aleman

et al. 2018

Cancer

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Background Hodgkin lymphoma (HL) survivors treated with abdominal radiotherapy and/or alkylating chemotherapy have an increased risk of colorectal cancer (CRC). This study was aimed at evaluating the prevalence of colorectal neoplasia in HL survivors. Methods This multicenter cohort study assessed the diagnostic yield of advanced colorectal neoplasia detected by a first surveillance colonoscopy among HL survivors treated with abdominal radiotherapy and/or procarbazine. Advanced colorectal neoplasia included advanced adenomas (high‐grade dysplasia, ≥25% villous component, or ≥10‐mm diameter), advanced serrated lesions (dysplasia or ≥10‐mm diameter), and CRC. The results were compared with those for a Dutch general population cohort that underwent a primary screening colonoscopy (1426 asymptomatic individuals 50‐75 years old). This study demonstrated the results of a predefined interim analysis. Results A colonoscopy was performed in 101 HL survivors, who were significantly younger (median, 51 years; interquartile range [IQR], 45‐57 years) than the general population controls (median, 60 years; IQR, 55‐65 years; P < .001). The prevalence of advanced neoplasia was higher in HL survivors than controls (25 of 101 [25%] vs 171 of 1426 [12%]; P < .001). Advanced adenomas were detected in 14 of 101 HL survivors (14%) and in 124 of 1426 controls (9%; P = .08). The prevalence of advanced serrated lesions was higher in HL survivors than controls (12 of 101 [12%] vs 55 of 1426 [4%]; P < .001). Serrated polyposis syndrome was present in 6% of HL survivors and absent in controls (P < .001). Conclusions HL survivors treated with abdominal radiotherapy and/or procarbazine have a high prevalence of advanced colorectal neoplasia. The implementation of a colonoscopy surveillance program should be considered.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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High prevalence of advanced colorectal neoplasia and serrated polyposis syndrome in Hodgkin lymphoma survivors

Rigter

Spaander

Aleman

et al. 2018

Cancer

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“…A difference in carcinogenesis has been suggested only for therapy‐related colorectal cancer diagnosed in HL survivors, as these tumors are more frequently microsatellite instable due to somatic mutations in mismatch repair genes . In therapy‐related esophageal cancer compared with sporadic cancer, no difference in frequency of microsatellite instability or loss of heterozygosity was found .…”

Section: Discussionmentioning

confidence: 99%

“…[3][4][5][6][7][9][10][11] A few studies suggest a difference in clinical and histopathological characteristics of GI cancer in HL survivors compared with first primary GI cancer. [12][13][14] To our knowledge, only one previous study examined survival of GI cancer in HL survivors and reported a worse overall survival in subgroups of HL survivors compared with first primary GI cancer patients, that is, those diagnosed with TNM stage IIB-IV colon cancer and a small group (N = 8) of TNM stage I gastric cancer. 13 No differences in disease-specific survival were found.…”

Section: Introductionmentioning

confidence: 99%

Overall and disease‐specific survival of Hodgkin lymphoma survivors who subsequently developed gastrointestinal cancer

et al. 2018

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BackgroundHodgkin lymphoma (HL) survivors have an increased risk of gastrointestinal (GI) cancer. This study aims to evaluate whether survival of patients who survived HL and developed GI cancer differs from survival of first primary GI cancer patients.MethodsOverall and cause‐specific survival of GI cancer patients in a HL survivor cohort (GI‐HL, N = 104, including esophageal, gastric, small intestinal, and colorectal cancer) was compared with survival of a first primary GI cancer patient cohort (GI‐1, N = 1025, generated by case matching based on tumor site, gender, age, and year of diagnosis). Cox proportional hazards regression was used for survival analyses. Multivariable analyses were adjusted for GI cancer stage, grade of differentiation, surgery, radiotherapy, and chemotherapy.ResultsGI‐HL cancers were diagnosed at a median age of 54 years (interquartile range 45‐60). No differences in tumor stage or frequency of surgery were found. GI‐HL patients less often received radiotherapy (8% vs 23% in GI‐1 patients, P < 0.001) and chemotherapy (28% vs 41%, P = 0.01) for their GI tumor. Compared with GI‐1 patients, overall and disease‐specific survival of GI‐HL patients was worse (univariable hazard ratio (HR) 1.30, 95% confidence interval (CI) 1.03‐1.65, P = 0.03; and HR 1.29, 95% CI 1.00‐1.67, P = 0.049, respectively; multivariable HR 1.33, 95% CI 1.05‐1.68, P = 0.02; and HR 1.33, 95% CI 1.03‐1.72, P = 0.03, respectively).ConclusionsLong‐term overall and disease‐specific survival of GI cancer in HL survivors is worse compared with first primary GI cancer patients. Differences in tumor stage, grade of differentiation, or treatment could not explain this worse survival.

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The resistance mechanisms and treatment strategies of BTK inhibitors in B‐cell lymphoma

Wang

Zhang

Yang

et al. 2021

Hematological Oncology

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Bruton's tyrosine kinase inhibitors (BTKi) have revolutionized the treatment of B-cell lymphoma (BCL). These drugs interfere with the mechanisms underlying malignant Bcell pathophysiology, allowing better drug response as well as low toxicity. However, these multiple mechanisms also lead to drug resistance, which compromised the treatment outcome and needs to be solved urgently. This review focuses on genomic variations (such as BTK and its downstream PCLG2 mutations as well as Del 8p, 2p+, Del 6q/8p, BIRC3, TRAF2, TRAF3, CARD11, MYD88, and CCND1 mutations) and related pathways (such as PI3K/Akt/mTOR, NF-κB, MAPK signaling pathways, overexpression of B-cell lymphoma 6, platelet-derived growth factor, toll-like receptors, and microenvironment, cancer stem cells, and exosomes) involved in cancer pathophysiology to discuss the mechanisms underlying resistance to BTKi. We have also reviewed the newly reported drug resistance mechanisms and the proposed potential treatment strategies (the next-generation BTKi, proteolysis-targeting chimera-BTK, XMU-MP-3, PI3K-Akt-mTOR pathway, MYC or LYN kinase inhibitor, and other small-molecule targeted drugs) to overcome drug resistance. The findings presented in this review lay a strong foundation for further research in this field.

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Double somatic mutations in mismatch repair genes are frequent in colorectal cancer after Hodgkin's lymphoma treatment

Abstract: We have demonstrated a higher frequency of MSI among t-CRCs, which results from somatic MMR gene mutations. This suggests a novel association of somatic MMR gene mutations with prior anticancer treatment.

Cited by 31 publications

References 53 publications

High prevalence of advanced colorectal neoplasia and serrated polyposis syndrome in Hodgkin lymphoma survivors

High prevalence of advanced colorectal neoplasia and serrated polyposis syndrome in Hodgkin lymphoma survivors

Overall and disease‐specific survival of Hodgkin lymphoma survivors who subsequently developed gastrointestinal cancer

The resistance mechanisms and treatment strategies of BTK inhibitors in B‐cell lymphoma

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