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Tuesday, August 23, 2016

PARP inhibition and gynecologic malignancies: A review of current literature and on-going trials



Abstract

 The poly (ADP-ribose) polymerase (PARP) family of enzymes is important in several DNA repair pathways. Drugs that inhibit these enzymes have been investigated in many types of cancer, but their application in the treatment of gynecologic malignancies has rapidly evolved - as manifested by the 2014 FDA approval for olaparib in the treatment of recurrent ovarian cancer associated with a germline BRCA mutation (gBRCA). In efforts to broaden their efficacy, current clinical trials have demonstrated benefit of olaparib, and other PARP inhibitors (PARPi), as single agents and in combination with cytotoxic chemotherapy and biologic agents, in wide ranging populations. Although the majority of data for PARPi in gynecologic malignancies has been specifically regarding ovarian cancer, their role in the treatment of uterine and cervical cancer is currently being investigated. This review will serve as a synopsis of seminal trials to date, summarize the breadth of clinical application in on-going studies, query how these results may change future practice, and reflect on questions yet to be answered.
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Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations | Cancer Research



 Definition of Pleiotropic - MedicineNet
Pleiotropic: Producing or having multiple effects from a single gene.
                                ~~~~~~~~~~~~~~~~~~~

abstract
Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations
AACR Prevention and Epidemiology
 on behalf of Ovarian Cancer Association Consortium (OCAC), on behalf of The PRACTICAL Consortium, on behalf of Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), on behalf of Colorectal Transdisciplinary (CORECT) Study, on behalf of African American Breast Cancer Consortium (AABC) and African Ancestry Prostate Cancer Consortium (AAPC)

 Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression.
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Pfizer buying Medivation in deal valued at about $14B (Update)



financial news

 Aside from Xtandi, Pfizer Inc. said Medivation also has a promising pipeline of cancer drugs in late-stage clinical development. That includes the potential breast cancer treatment talazoparib and a potential lymphoma drug.

Medivation website:
Talazoparib
Overview
Talazoparib, an orally available poly-ADP ribose polymerase, or PARP, inhibitor, is currently in a Phase 3 clinical trial for the treatment of patients with gBRCA mutated breast cancer (i.e., advanced breast cancer in patients whose BRCA genes contain germline mutations). In addition, we are targeting a number of other solid tumor indications in which to investigate talazoparib, including breast (beyond gBRCA mutations), prostate, small cell lung, and ovarian cancers.
                         ~~~~~~~~~~
Note: gBRCA = BRCA1/2
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Researchers discover otulipenia, a new inflammatory disease



medical news
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Monday, August 22, 2016

JCO search "ovarian" 10 recent articles - results eg. recap



Search Results

 Searching journal content for ovarian in full text.
  1. CORRESPONDENCE Population Frequency of Germline BRCA1/2 Mutations JCO published online on August 22, 2016; DOI:10.1200/JCO.2016.67.0554.
    ...highly penetrant for hereditary breast and ovarian cancer syndrome, with lifetime risks-dependent...to 70% for breast and 15% to 55% for ovarian cancer. 2 BRCA1/2 mutations also lead...high-risk familial hereditary breast and ovarian cancer may not be applicable in the discussion...
  2. CORRESPONDENCE Reply to S.M. Sorscher and M.J. Hall et al JCO published online on August 22, 2016; DOI:10.1200/JCO.2016.69.1022.
    ...without a known family history of breast or ovarian cancer. 8 Whereas Axilbund questions...mutations has been demonstrated in epithelial ovarian cancers 13 ; however, it is still not...mutations significantly increase the risk of ovarian cancer, and if so, by how much. Only...
  3. CORRESPONDENCE Multigene Panels to Evaluate Hereditary Cancer Risk: Reckless or Relevant? JCO published online on August 22, 2016; DOI:10.1200/JCO.2016.68.6725.
    ...management, both women were counseled about increased BC and ovarian cancer risks conferred by BRCA1/2 and were offered follow-up...actionability of multigene panel testing for hereditary breast and ovarian cancer risk assessment. JAMA Oncol 1:943-951, 2015...
  4. CORRESPONDENCE Reply to M.J. Hall et al and K.N. Maxwell et al JCO published online on August 22, 2016; DOI:10.1200/JCO.2016.69.1964.
    ...were developed primarily on the basis of penetrance in families that were phenotypically consistent with hereditary breast and ovarian cancer or Lynch syndrome, respectively. It remains to be seen what the penetrance ranges will be in patients and/or families...
  5. ORIGINAL REPORTS - Epidemiology Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium JCO Aug 20, 2016:2888-2898; DOI:10.1200/JCO.2016.66.8178.
    ...REPORTS Epidemiology EPID1 EPID3 GYNC15 Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium Nicolas Wentzensen...understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention...
  6. ORIGINAL REPORTS - Gynecologic Cancer Randomized Phase III Trial of Irinotecan Plus Cisplatin Compared With Paclitaxel Plus Carboplatin As First-Line Chemotherapy for Ovarian Clear Cell Carcinoma: JGOG3017/GCIG Trial JCO Aug 20, 2016:2881-2887; DOI:10.1200/JCO.2016.66.9010.
    ...Carboplatin As First-Line Chemotherapy for Ovarian Clear Cell Carcinoma: JGOG3017/GCIG...demonstrates poor outcomes in epithelial ovarian cancer. The Japanese Gynecologic Oncology...improving the prognosis of CCC. INTRODUCTION Ovarian cancer is the seventh most common cancer...
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Correspondence: Where Are We Headed With Research in Frail Elderly Patients With Cancer?



Where Are We Headed With Research in Frail Elderly Patients With Cancer?

 We should ask ourselves two key questions: Are we properly identifying the frail elderly patient with cancer who comes to our consulting rooms? And do we have sufficient scientific evidence to decide whether to treat this patient with chemotherapy? If we want to treat this population group to the best of our ability, we should be able to answer these questions.
 To the Editor:
The article by Corre et al1 described the ESOGIA (Elderly Selection on Geriatric Index Assessment) trial that was carried out in French and Spanish hospitals and that included elderly patients age 70 years or older with advanced non–small-cell lung cancer. The article provides hitherto unpublished information about the ability of a comprehensive geriatric assessment (CGA) to classify elderly patients with cancer and about its usefulness in decision making in this age group. CGA has already demonstrated its superiority in evaluating the elderly by providing more information than simply the patient’s performance status2 and by giving a more reliable prediction of the risk of toxicity with chemotherapy.3,4 In addition, different components of the CGA have independently demonstrated its ability to predict the toxicity of chemotherapy.3-5 Recently, the oncological-multidimensional prognostic index (Onco-MPI), which is based on the CGA, has proved to be a good predictive tool for 1-year mortality in older patients with cancer.6 Despite many relevant advances, it seems that not all of the efforts to reach a specific and definitive conclusion with regard to selecting treatment for elderly patients with cancer are heading in the same direction.....


REFERENCES

  1. 1.↵

    1. Corre R,
    2. Greillier L,
    3. Le Caër H,
    4. et al.
    (2016) Use of a comprehensive geriatric assessment for the management of elderly patients with advanced non–small-cell lung cancer: The phase III randomized ESOGIA-GFPC-GECP 08-02 study. J Clin Oncol 34:1476–1483.

    Abstract/FREE Full Text
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Correspondence (+links): Population Frequency of Germline BRCA1/2 Mutations



Population Frequency of Germline BRCA1/2 Mutations
 

To the Editor:

Knowledge of BRCA1/2 mutation status plays an important role in multiple aspects of oncologic care.1 Inherited mutations in BRCA1/2 are highly penetrant for hereditary breast and ovarian cancer syndrome, with lifetime risks—dependent upon the gene and population—of 50% to 70% for breast and 15% to 55% for ovarian cancer.2 BRCA1/2 mutations also lead to increased risks of other malignancies, such as prostate, pancreatic, and male breast cancers, although penetrance is lower.
Germline BRCA1/2 testing has traditionally been guided by personal and family cancer history1; however, two developments are changing the landscape of BRCA1/2 testing. First, the increased use of tumor genomic sequencing is leading to identification of germline BRCA1/2 mutations in patients without typical personal or family histories.3 Tumor genomic sequencing panels that contain BRCA1/2 that do not subtract matched germline DNA are fundamentally opportunistic screenings of patients with cancer. Second, for populations with a high frequency of BRCA1/2 mutation carriers,4 screening of all individuals has been proposed.5 For consideration of population-based BRCA1/2 testing, the expected frequency of a positive result is a required piece of critical information.....

 Fig 1. Graphical representation of BRCA1/2 heterozygous population frequencies in Exome Variant Server (EVS) and Exome Aggregation Consortium (ExAC) databases.

 Furthermore, population frequencies and penetrance estimates obtained from patients with high-risk familial hereditary breast and ovarian cancer may not be applicable in the discussion of population-based BRCA1/2 testing.
 

REFERENCES

  1. 1.↵
    1. Daly MB,
    2. Pilarski R,
    3. Axilbund JE,
    4. et al.
    (2014) Genetic/familial high-risk assessment: Breast and ovarian, version 1.2014. J Natl Compr Canc Netw 12:1326–1338.
    Abstract/FREE Full Text
  2. 2.↵
    1. Mavaddat N,
    2. Peock S,
    3. Frost D,
    4. et al.
    (2013) Cancer risks for BRCA1 and BRCA2 mutation carriers: Results from prospective analysis of EMBRACE. J Natl Cancer Inst 105:812–822.
    Abstract/FREE Full Text
  3. 3.↵
    1. Schrader KA,
    2. Cheng DT,
    3. Joseph V,
    4. et al.
    (2016) Germline variants in targeted tumor sequencing using matched normal DNA. JAMA Oncol 2:104–111, [Erratum: JAMA Oncol 2:279, 2016].
    CrossRefMedlineGoogle Scholar
  4. 4.↵
    1. Gabai-Kapara E,
    2. Lahad A,
    3. Kaufman B,
    4. et al.
    (2014) Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2. Proc Natl Acad Sci USA 111:14205–14210.
    Abstract/FREE Full Text
  5. 5.↵
    1. King MC,
    2. Levy-Lahad E,
    3. Lahad A
    (2014) Population-based screening for BRCA1 and BRCA2: 2014 Lasker Award. JAMA 312:1091–1092.
    CrossRefMedlineGoogle Scholar
  6. 6.↵
    1. Anglian Breast Cancer Study Group
    (2000) Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Br J Cancer 83:1301–1308.
    CrossRefMedline
  7. 7.↵
    1. Thompson ER,
    2. Rowley SM,
    3. Li N,
    4. et al.
    (2016) Panel testing for familial breast cancer: Calibrating the tension between research and clinical care. J Clin Oncol 34:1455–1459.
    Abstract/FREE Full Text
  8. 8.↵
    1. National Heart, Lung, and Blood Institute
    NHLBI exome sequencing project (ESP): Exome variant server. http://evs.gs.washington.edu/EVS/.
  9. 9.↵
    1. Exome Aggregation Consortium
    ExAC browser (beta). http://exac.broadinstitute.org.
  10. 10.↵
    1. Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
    The Netherlands. https://enigmaconsortium.org/wp-content/uploads/2016/06/ENIGMA_Rules_2015-03-26.pdf.

Related Articles

  • CORRESPONDENCE: Reply to S.M. Sorscher and M.J. Hall et al
    • Nadine M. Tung and
    • Judy E. Garber
    JCO JCO691022; published online on August 22, 2016;
  • CORRESPONDENCE: Multigene Panels to Evaluate Hereditary Cancer Risk: Reckless or Relevant?
    • Michael J. Hall,
    • Elias Obeid,
    • and Mary B. Daly
    JCO JCO686725; published online on August 22, 2016;
  • CORRESPONDENCE: Next-Generation Sequencing of Tumors to Better Estimate the Clinical Significance of Non-BRCA Germline Deleterious Mutations
    • Steven M. Sorscher
    JCO JCO677724; published online on August 22, 2016;
  • CORRESPONDENCE: Reply to M.J. Hall et al and K.N. Maxwell et al
    • Jennifer E. Axilbund
    JCO JCO691964; published online on August 22, 2016;
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Letter: Multigene Panels to Evaluate Hereditary Cancer Risk: Reckless or Relevant?



Multigene Panels to Evaluate Hereditary Cancer Risk: Reckless or Relevant?

  To the Editor:
A recent editorial by Axilbund1 accompanies two important studies of hereditary multiple gene panel tests conducted in patients with breast cancer (BC).2,3 In one study, by Tung et al,2 488 women with incident BC were tested with a commercial non–BC-specific 25-gene panel. Mutations were identified in 10.7% patients, including 4.6% outside of BRCA1/2 in predominantly moderate penetrance BC genes, such as CHEK2, ATM, and BRIP1. Of interest, 4 (7.3%) mutations were in genes not associated with BC, including one mutation each in the Lynch syndrome (LS) genes, MSH6 and PMS2. In the second study, Thompson et al3 used case-control analysis of nearly 4,000 BRCA1/2-negative BC cases and controls and showed that mutation frequency was significantly increased for just two of 18 genes (PALB2 and TP53) included on a commercial hereditary BC panel. Strikingly, the rate of mutations in controls was more than one half that of cases (2.3% v 4.0%), and mutation carriers were identified among controls for 12 of 18 genes. Together, these studies demonstrate the improved diagnostic breadth offered by panel tests, and, yet, the high rate of mutations among control participants casts doubt on the power of panel tests enriched in moderate penetrance genes to effectively distinguish between those patients who will develop BC from those who will not...

  1. Axilbund JE
(2016) Panel testing is not a panacea. J Clin Oncol 34:1433–1435.
FREE Full Text

Michael J. Hall

Patents, Royalties, Other Intellectual Property: Shares a patent with several Fox Chase investigators for a novel method to investigate hereditary colorectal cancer genes (Inst)
Travel, Accommodations, Expenses: PAREXEL International, Myriad Genetics
Other Relationship: Myriad Genetics, Foundation Medicine, Invitae
Previous SectionNext Section

Elias Obeid

Consulting or Advisory Role: Merck Sharpe and Dohm
Research Funding: Myriad Genetics, Merck, Genentech, Pfizer
Previous SectionNext Section

Mary B. Daly

No relationship to disclose
Previous Section
 

REFERENCES

  1. 1.↵
    1. Axilbund JE
    (2016) Panel testing is not a panacea. J Clin Oncol 34:1433–1435.
    FREE Full Text
  2. 2.↵
    1. Tung N,
    2. Lin NU,
    3. Kidd J,
    4. et al.
    (2016) Frequency of germline mutations in 25 cancer susceptibility genes in a sequential series of patients with breast cancer. J Clin Oncol 34:1460–1468.
    Abstract/FREE Full Text
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Response: Multigene panels to evaluate hereditary cancer risk: Reckless or relevant?



Reply to M.J. Hall et al and K.N. Maxwell et al

Hall et al1 call for testing BRCA1/2 and Lynch syndrome genes in all patients with breast cancer and/or colorectal cancer who undergo genetic testing, regardless of whether the family history is consistent with both syndromes. The literature on frequency of unexpected findings on broad panel tests is growing rapidly, but there remains a paucity of data on the penetrance of historically high-risk genes when variants are identified in individuals and families who are not suggestive of the associated syndrome. Current guidelines for the management of patients with pathogenic variants in BRCA1/2 and Lynch syndrome genes were developed primarily on the basis of penetrance in families that were phenotypically consistent with hereditary breast and ovarian cancer or Lynch syndrome, respectively. It remains to be seen what the penetrance ranges will be in patients and/or families who are essentially undergoing genetic screening for syndromes for which their reported diagnosis and history is not presently suggestive......


REFERENCES

  1. 1.↵
    Hall MJ, Obeid E, Daly MB: Multigene panels to evaluate hereditary cancer risk: Reckless or relevant? J Clin Oncol 10.1200/JCO.2016.68.6725.
  2. 2.↵
    Maxwell KN, Domchek SM, Nathanson KL, et al: Population frequency of germline BRCA1/2 mutations. J Clin Oncol 10.1200/JCO.2016.67.0554.
  3. 3.↵
    1. Robson ME,
    2. Bradbury AR,
    3. Arun B,
    4. et al.
    (2015) American Society of Clinical Oncology policy statement update: Genetic and genomic testing for cancer susceptibility. J Clin Oncol 33:3660–3667.
    Abstract/FREE Full Text
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Psychosocial Adjustment and Perceived Risk Among Adolescent Girls From Families With BRCA1/2 or Breast Cancer History



abstract:
Psychosocial Adjustment and Perceived Risk Among Adolescent Girls From Families With BRCA1/2 or Breast Cancer History


Purpose To evaluate the impact of breast cancer family history and maternal BRCA1/2 mutation on the psychosocial adjustment and perceived risk in girls age 11 to 19 years old. 

Materials and Methods Girls age 11 to 19 years old with one or more relatives with breast cancer or a familial BRCA1/2 mutation (breast cancer family history [BCFH] positive, n = 208; n = 69 with BRCA1/2-positive mother), peers (BCFH negative, n = 112), and their mothers completed assessments of psychosocial adjustment, breast cancer–specific distress, and perceived risk of breast cancer. 

Results General psychosocial adjustment did not differ significantly between BCFH-positive and BCFH-negative girls, either by self-report or mother report, except for higher self-esteem among BCFH-positive girls (P = .01). BCFH-positive girls had higher breast cancer–specific distress than BCFH-negative girls (P < .001), but girls from BRCA1/2-positive families did not differ from other BCFH-positive peers. BCFH-positive girls were more likely to report themselves at increased self-risk for breast cancer in adulthood than BCFH-negative peers (74% v 33%, respectively; P ≤ .001). Girls from BRCA1/2-positive families were more likely than other BCFH-positive and BCFH-negative peers to report themselves at increased risk (P < .001). In all groups, perceived risk of breast cancer was associated with older age. Higher breast cancer–specific distress among adolescent girls was associated with higher self-perceived risk of breast cancer and higher maternal breast cancer–specific distress. 

Conclusion Adolescent girls from BRCA1/2-positive and breast cancer families have higher self-esteem and do not have poorer psychosocial adjustment than peers. However, they do experience greater breast cancer–specific distress and perceived risk of breast cancer, particularly among older girls. Understanding the impact is important to optimize responses to growing up in families at familial and genetic risk for breast cancer, particularly given the debate over the genetic testing of children for cancer susceptibility in adulthood.
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The impact of lymph node dissection and adjuvant chemotherapy on survival: A nationwide cohort study of patients with clinical early-stage ovarian cancer



abstract

Highlights
In early stage ovarian cancer:
•
Lymph node dissection improves relative survival.
•
Chemotherapy after adequate lymph node dissection does not improve survival also in case of high-risk features.
•
Preferably 20 or more lymph nodes should be removed for an adequate staging.

Introduction

To establish the impact of lymph node dissection and chemotherapy on survival in patients with early-stage epithelial ovarian cancer (EOC).

Methods

All Dutch patients with International Federation of Gynaecology and Obstetrics (FIGO) stage I–IIA and IIIA1 EOC between 2000 and 2012 were included. Data concerning age, stage, tumour grade, histological subtype, hospital type, lymph node dissection, adjuvant chemotherapy and survival were extracted from the Netherlands Cancer Registry.

Results

Of 3658 patients included, 1813 (49.6%) had lymph nodes removed. Relative survival of patients with lymph node dissection (including those with lymph node metastases) was significantly better than that of patients without, also after correcting for stage, tumour grade, histology and age (89% and 82%, respectively; relative excess risk [RER], 0.64; 95% confidence interval [CI]: 0.52–0.78). There was a positive correlation between the number of removed lymph nodes and overall survival (after excluding patients with lymph node metastases). Of patients with stage I–IIA EOC who had ≥10 lymph nodes removed, there was no difference in relative survival between those who received chemotherapy and those who did not (RER, 0.51; 95% CI: 0.15–1.64). This was also true for a subgroup of patients with high-risk features (stage IC and IIA and/or tumour grade 3 and/or clear cell histology [RER, 0.90; 95% CI: 0.46–1.99]).

Conclusion

Adequate dissection of at least 10 but preferably ≥20 lymph nodes should be standard procedure for the staging of early-stage EOC. Adjuvant chemotherapy after an adequate lymph node dissection does not seem to contribute to a better relative survival.
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Gender differences in the effect of grief reactions/burnout on emotional distress among clinical oncologists (Israel/Canada)



abstract


BACKGROUND

The current study was conducted to examine gender differences in the effect of grief reactions and burnout on emotional distress among clinical oncologists.

METHODS

The participants included a convenience sample of 178 oncologists from Israel (52 of whom were women) and Canada (48 of whom were women). Oncologists completed a questionnaire package that included a sociodemographic survey, the General Health Questionnaire, a burnout measure, and the Adult Oncologists Grief Questionnaire. To examine the effect of grief reactions and burnout on emotional distress while controlling for country and past depression within each gender, 2 hierarchical linear regression analyses were computed.

RESULTS

Female oncologists reported significantly more grief responses to patient death (mean, 47.72 [standard deviation (SD), 8.71] and mean, 44.53 [SD, 9.19], respectively), more emotional distress (mean, 12.41 [SD, 4.36] and mean, 10.64 [SD, 3.99], respectively), and more burnout (mean, 2.59 [SD, 1.69] and mean, 1.84 [SD, 1.5], respectively). For both genders, higher levels of grief reactions were associated with greater emotional distress among those who reported high levels of burnout (P<.001). However, for men, the association between grief reactions and emotional distress also was documented at moderate levels of burnout (P<.001).

CONCLUSIONS

Patient death is a regular part of clinical oncology. It is essential that oncologists be able to cope effectively with this aspect of their work. The findings of the current study highlight the need to take into account the cumulative stressors that oncologists contend with when designing supportive interventions. Gender differences in burnout, reactions to patient death, and emotional distress need to be addressed to ensure the best quality of life for oncologists and the best quality of care for their patients.
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Sunday, August 21, 2016

IDH1 mutated low grade astrocytoma occurring in MSH2 mutated Lynch syndrome family



open access (pdf)
open access (text)



Lynch syndrome (LS) is an autosomal dominant tumour predisposition syndrome caused by a germline mutation in one of the DNA mismatch repair (MMR) genes. Patients with these mutations have an increased risk of brain tumours, the vast majority of which are glioblastomas and medulloblastomas, and their occurrence has been termed Turcot Syndrome. The case presented herein of a member of a Lynch syndrome family with an MSH2 mutation expands the spectrum of brain tumours occurring in Lynch syndrome to include low grade astrocytomas,
and is the first reported case of an IDH1 (R132H) mutated brain tumour occurring in a Lynch syndrome family.

 Patients with a pathogenic DNA MMR gene mutation have a 10–50% risk for developing colorectal carcinoma at an early age (mean 45–50 years) and extracolonic malignancies can occur including endometrial, ovarian, hepatic, pancreatic and ureteric carcinomas and brain tumours [1] and [2]. Although the 1–3% lifetime risk of brain tumours is low compared to other extracolonic tumours in LS families [1], this risk is 6 fold that of the general population and its occurrence has been termed Turcot Syndrome. The brain tumours previously described in Lynch/Turcot syndrome have mostly been high grade gliomas, predominantly glioblastomas, and less commonly, medulloblastomas [1], [3], [4], [5] and [6]. A recent European study described the risk of developing brain tumours being highest (2.5%) in Lynch syndrome patients with MSH2 mutations, contained the first description of low grade astrocytoma in Lynch syndrome (1/47 gliomas was a pilocytic astrocytoma (WHO grade I), and 1/47 was a diffuse astrocytoma (WHO grade II)), and showed universal negativity for mIDH1 immunoreactivity in Lynch syndrome associated glioma [7].The present case adds to the sparse literature on low grade astrocytomas in Lynch syndrome and is the first report of a Lynch syndrome associated IDH1 R132H mutated glioma....
 

4. Discussion

There are two unique aspects to our case.First, low grade astrocytoma histology has only rarely been previously reported in LS families [6] and [7].Second, to our knowledge, this is the first case of IDH1 mutated glioma reported in the setting of an LS family [8] and [9].Whether the presence of a mutated IDH1 glioma in a patient with MSH2 mutation is a chance occurrence or is informative about oncogenesis remains uncertain.

5. Conclusion

Brain tumours reported in Lynch syndrome families have predominantly been glioblastoma or medulloblastoma, and the present case expands this spectrum to include mIDH1 (R132H) mutated low grade astrocytoma.
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I Stand Up To Cancer - Who Do You Stand Up for?



I Stand Up To Cancer

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